NEW YORK — In July 1992, the Sicilian Mafia sent a loud and gruesome message to those who would challenge it when it killed a prosecutor named Paolo Borsellino with a car bomb in Palermo. He was the second prosecutor to meet that fate in two months; in May, another bomb had killed Giovanni Falcone.

The assassinations made news around the world, and the second one made the Mafia a new enemy: Rita Borsellino, Paolo’s younger sister. Before her brother’s death she was a pharmacist. After it, she became a leading crusader against the Mafia’s longstanding, often ruthless grip on life in Sicily, where small businesses were routinely extorted for protection money and killings were commonplace.

Ms. Borsellino was often frustrated over the years as she waged that fight. In 2006 she ran for governor of Sicily and lost to Salvatore Cuffaro, the incumbent, who had been linked to the Mafia and later went to prison. In 2009 at an anti-Mafia march, she told Agence France-Presse, “I am angry and less optimistic than 17 years ago, when my brother was slain.’’ Mafia influence remains a vexing problem in Sicily and elsewhere in Italy.

Yet Ms. Borsellino, who died Wednesday in Palermo at 73 after what Italian newspapers said was a long illness, lived to see some successes as well. Among others was that when Salvatore Riina, the head of Sicily’s notorious Cosa Nostra crime syndicate and the man who ordered the murders of the two prosecutors, died last year, he was serving 26 life sentences.

Ms. Borsellino’s death was announced on the website of Libera, an association of organizations working to combat Mafia influence of which she was founding vice president, serving in that role from 1995 to 2005.

Ms. Borsellino was born on June 2, 1945, in Palermo. There had been pharmacists in her family stretching back several generations, and she followed the tradition, earning a pharmaceutical degree in 1967.

While she was pursuing her career, her brother was becoming a thorn in the side of the Mafia, so much so that he traveled with bodyguards. Five of them were killed in the bombing that killed him, as he arrived for a visit with his mother.

The Borsellino and Falcone murders produced a wave of outrage, as well as swift action by the Italian government, which sent troops to Sicily in an effort to restore order. The troops stayed for six years.

During that time Ms. Borsellino emerged as the face of the anti-Mafia movement. After her brother’s death she began speaking in schools, talking to children about ethics and civic responsibility. She also worked with Arci, another group that tries to combat Mafia influence.

Geoff Andrews, a senior lecturer in politics at the Open University and the author of “Not a Normal Country: Italy After Berlusconi,’’ said Ms. Borsellino “was a symbol of resistance for a new generation of anti-Mafia activists.’’

“Yet,’’ he added, “she was more than a historic reference point of the events of 1992. She had the commitment and vision to help build a new dialogue between civil society and politicians with roots in the local associations, including the anti-Mafia network Libera, and not the traditional parties. She had the vision to appeal to younger Sicilians who wanted a new beginning.’’

Ms. Borsellino was not afraid to criticize authority. When the Italian government withdrew the troops from Sicily in 1998, she was skeptical.

“For those of us who have lived it, the emergency is not over,’’ she told The New York Times that year. “The soldiers had a deterrent effect, and they symbolized the active presence of the state. The war is still going on, so why stop now?’’

She even criticized Pope Benedict XVI. In 2010, when he gave a homily in Sicily that anti-Mafia forces hoped would be a ringing denunciation of the Cosa Nostra, she was among those who found his words too timid.

“I was disappointed in the lack of force in what he said,’’ she told Reuters.

Ms. Borsellino was a member of the European Parliament from 2009 to 2014. She was named to its Special Committee on Organized Crime in 2012, giving her a chance to work on organized crime’s growing influence throughout Europe, something she had voiced concerns about in an interview several years earlier.

“The Mafia is no longer an Italian problem,’’ she said. “It has definitely become a European issue. I would say even a worldwide or international issue. In the last few years, they have changed their trafficking and their routes, their contacts, their financial and commercial links. To symbolize the extent of the change, we no longer speak of ‘the Mafia’ today, but of ‘mafias.’ ’’

The biography on Ms. Borsellino’s Facebook page says she was married and the mother of three children, but complete information on her survivors was not immediately available.

In 2010, to mark the 18th anniversary of the 1992 assassinations, statues of Ms. Borsellino’s brother and Falcone were placed in a public square in Palermo. Within hours they had been vandalized, and Ms. Borsellino had withering words in response to both the vandalism and to the lack of witnesses willing to come forward.

“There are people in Palermo who are frightened even of two statues,’’ she said, “and, what is more, there are still people in Palermo who don’t have the gift of speech.’’