Police said officers were called to the incident in Marine Parade near Burlington Street just before 1am.
A police spokesman said: "The 15-year-old boy from Brighton was rushed to the Royal Sussex County Hospital, but was declared dead at 1.19am. His family has been informed."
Police at the scene said no arrests had been made. The road was closed for investigation work for several hours.
Brighton and Hove buses has said it has opened a 'thorough internal investigation' into the collision and its staff were 'very saddened' by the incident.
Witnesses are asked to contact the serious collision investigation unit on 101 quoting Operation Rivington.