February 22, 2017 1256 GMT
According to the statement from the White House, retired Lieutenant General Keith Kellog was appointed instead of Flynn.
"President Donald J. Trump has named Lt. General Joseph Keith Kellogg, Jr. (Ret) as Acting National Security Advisor following the resignation of Lt. General Michael Flynn (Ret)," the statement said.
CNN reported Monday that Flynn's resignation could be related to his contacts with Russia.
Earlier in the day, Trump was said to be looking into the situation involving National Security Advisor Mike Flynn regarding reports of his pre-inaugural phone calls with Russian Ambassador to the United States Sergey Kislyak.
Flynn’s phone communications with Kislyak prior to Trump’s inauguration on January 20 have raised questions about whether the advisor broke a law forbidding private US citizens from engaging with foreign nations about diplomatic disputes.
US media reported Flynn had discussed the issue of anti-Russian sanctions with Kislyak before Trump was officially sworn in as US president.