"We have to come to a stage where we cannot keep searching for something we cannot find," Mahathir told a news conference.
"If we find any new information, we may resume the search," he said.
Flight MH370, carrying 239 people, vanished on a flight from Kuala Lumpur to Beijing on March 8, 2014, becoming one of the world's greatest aviation mysteries.
A privately funded underwater search for the missing jet ended on Tuesday.
(Reporting by Rozanna Latiff; Writing by Praveen Menon; Editing by Robert Birsel)