The Airbus A380 super jumbo, carrying 263 passengers, landed safely at Singapore's Changi airport, an airline spokesman said.
The passengers were transferred to another flight which took off at 0900 GMT.
"The Airbus A380 Flight SQ866 from Singapore to Hong Kong returned to Changi Airport this afternoon as a result of a cockpit warning relating to a cargo door," the Singapore Airlines (SIA) spokesman said.
"SIA engineers are currently troubleshooting to find out the cause of why the warning came on," he added.
SQ866 is a daily flight from Singapore to Hong Kong that usually departs at 0500 GMT.
Singapore Airlines has 19 A380s with five others on order, operating on routes from Singapore to various destinations including Hong Kong, Frankfurt, London and Los Angeles.
In January, one of the airline's A380 fleet was forced to make an emergency landing in Azerbaijan after suffering a drop in cabin pressure. The flag-carrier subsequently said its investigation into the incident was focusing on a main deck door that appeared to have suffered a leak.
More than 120 A380s are in operation worldwide following the launch of the Airbus flagship super jumbo in 2007.
With PTI inputs,