The boat, carrying four females and two males, was returning to Wewak on Saturday (March 4) after their betelnut sales run to Lorengau.
A Manus woman is amongst those missing while the rest are from Tarawai Island, Murik and Maprik in the East Sepik Province.
Acting provincial police commander, Senior Inspector David Yapu, told Loop PNG the missing boat was reported on Friday 10 March after it did not reach Wewak.
This is the second time a boat on a betelnut run between Manus and Wewak did not reach its destination and PPC Yapu said his main concern is the safety of the passengers on board.
The first incident occurred in February 2016 when nine people went missing between Manus and Wewak after their betelnut sales in Lorengau. They have never been found.
He warned people to take extra precaution when travelling out at sea, especially at this time when the weather is bad with rough sea and strong wind.
National Disaster and Emergency Services, National Maritime Safety Authority and the other agencies have been alerted on the situation.