The Oscar-winning actor has been a vocal opponent of Mr Trump, saying he wanted to "punch him in the face" during the election campaign.
At the Los Angeles premiere of his new film The Comedian on Friday, De Niro said, "I'm very depressed.
"We have to just wait and see how things go. We have to keep our eyes and (be) ever vigilant on the government."
Asked whether people should protest against Mr Trump, De Niro replied, "Yes absolutely. If things aren't being done right, absolutely."
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