Departing from a strict US and Western policy of not talking with Assad, Hammond expressed concerns over Russia's role in the country, which has been torn apart by four years of civil war.
"Assad must go, he can't be part of Syria's future," Hammond said, according to Le Monde's French translation of the interview.
He added: "If we reach a deal on a transition authority and Assad is part of it, then it will be necessary to talk with him in his capacity as an actor in this process."
Hammond discussed Syria with his French and German counterparts in Paris on Thursday night, as the war in Syria takes center-stage in a series of meetings due to continue at the United Nations General Assembly in New York.
Russia has built up its military forces in Syria in recent weeks with combat aircraft, tanks and other equipment, sparking concerns in Washington and European capitals, which are pressing Moscow to clarify its intentions.
"Russia's military build-up complicates the situation," Hammond told Le Monde.
US President Barack Obama will push Russian President Vladimir Putin to explain how his country's military presence in Syria will contribute to defeating ISIS when the two leaders meet next week, White House officials said on Thursday.
Moscow wants its long-time ally Damascus to be included in the efforts to combat ISIS and says any international military operation in Syria should have a UN mandate.
Syrian government forces used newly arrived Russian warplanes to bombard ISIS insurgents in Aleppo province in northern Syria, a group monitoring the civil war said on Thursday; Reuters reported.