Dozens of human rights and anti-trafficking organizations will participate in the protest, scheduled for noon outside 1381 Ninth Ave.
The groups will be asking Craigslist to remove its "Adult Services" section, which they say encourages sexual exploitation.
Norma Ramos, executive director of the Coalition Against Trafficking in Women, said Craigslist has "defied and defeated" state attorneys general, a lawsuit, and members of Congress who have tried to take on the company.
"Nothing seems to get the message to this company that they are contributing to human trafficking in a very significant way, so we are bringing this message to their doorstep," Ramos said.
A spokesperson for Craigslist was not immediately available for comment.
Ramos said the protest will feature picket lines, signs and a handful of speakers, including authors Aaron Cohen and Victor Malarek, and actress Terria Joseph, who is the mother of singer Alicia Keys.
She said she hopes the protest will convince the company to change its policy.
"It's a very simple request: stop hosting these ads, which are being used to facilitate human trafficking," Ramos said.
A group of sex workers is also headed to Craigslist headquarters today for a counterprotest, said Rachel West, a spokeswoman for the US PROStitutes Collective.
The human rights groups are asking for a change that West said would put more women in danger rather than save them from exploitation.
"It's pushing prostitution underground and making women more vulnerable to rape, violence and arrest," she said. "By closing down ways for women to be able to advertise, and working more safely indoors, we'll put women in more vulnerable positions."
Craigslist gets more than 20 billion page views per month, the seventh-highest total worldwide among English-language sites, and has more than 50 million users in the U.S. alone, according to the company's website.