Senator Leila de Lima invoked a famous "People Power" revolution that toppled dictator Ferdinand Marcos three decades ago, in her strongest comments yet against Duterte and his drug war that has claimed thousands of lives.
"There is no more doubt that our president is a murderer and sociopathic serial killer," De Lima told reporters, as she called on cabinet to declare him unfit to lead, and asked ordinary Filipinos to voice their opposition to his rule.
If the cabinet members did not, De Lima referred to the mass uprising that ended the "iron fist" of Marcos's dictatorship in 1986.
"Now the time has come again for us to be brave and stand up to another criminal dictator and his evil regime," De Lima said.
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The government last week charged De Lima, a former national human rights commissioner, with orchestrating a drug trafficking ring when she was justice secretary in the previous administration.
She could be detained anytime, although the courts hearing the cases must issue an arrest warrant.
When asked about De Lima's comments, presidential spokesman Ernesto Abella simply described them as "colourful language" and pointed out that Duterte would allow public demonstrations against him.
Duterte, 71, won presidential elections last year after promising during the campaign to eradicate drugs in society by killing tens of thousands of people.
Amnesty International has warned police actions in the drug war may amount to crimes against humanity.
The powerful Roman Catholic Church, which helped lead the People Power revolution, has in recent months begun speaking out against the drug war and on Saturday held a rally against the killings, attracting thousands of people.