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"Facebook is the new cigarettes," Benioff told journalist Kara Swisher for an MSNBC special, "Revolution: Salesforce Changing the World," which will air on Sunday at 10 p.m. ET.
"You know, it's addictive. It's not good for you. There's people trying to get you to use it that even you don't understand what's going on. The government needs to step in. The government needs to really regulate what's happening," he said.
Benioff is not known to shy away from clashes with fellow tech leaders. Most recently, he successfully advocated for San Francisco to pass Proposition C, a tax on the city's biggest businesses meant to raise funds for the homeless. This put him in direct opposition to several of his peers, including Twitter and Square CEO Jack Dorsey, who argued the tax would disproportionately impact financial services companies like Square.
Benioff expressed concern over Facebook's impact on children in particular. When Swisher pushed back on the comparison of Facebook to deadly cigarettes, Benioff stood by his assessment.
"Well, I think this is ... the right comparison that we can see that, you know, Facebook can have very serious effects on society the same way that cigarettes can," he said.
It's not the first time Benioff has compared Facebook to the tobacco industry. In an interview on CNBC's "Squawk Alley" in January, Benioff said Facebook should be regulated, just like tobacco.
"I think that you do it exactly the same way that you regulated the cigarette industry. Here's a product: Cigarettes. They're addictive, they're not good for you," Benioff said at the time. "I think that for sure, technology has addictive qualities that we have to address, and that product designers are working to make those products more addictive and we need to rein that back."