It was discovered at an address associated with the actor around 5 a.m. near Greenwich and Franklin streets. Several streets in the area were closed, but have since reopened.
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Newscopter 7 is over the scene. The Tribeca Grill, owned by De Niro, is also located there.
Police decided to move the package to the NYPD's facility at Rodmans Neck in the Bronx for further investigation.
TIMELINE: Suspicious packages found in New York, D.C., elsewhere
Security personnel at Tribeca Productions summoned police and a bomb squad removed the package.
The company said in a statement on Thursday that its Manhattan building is open and deemed safe.
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The package sent to De Niro was identical to other packages received by high-profile democrats and CNN this week.
It used the same manila envelope, same stamps, and had the same return address to Debbie Wasserman Schultz.