The shooting will lead to renewed debate about France's gun laws, which have been brought into public focus by the shooting of seven people in March by an Islamic extremist in Toulouse and a spate of gang murders.
Police chief Herve Malherbe said the gunman killed a nightclub employee and customer at about 3am before fleeing the scene.
He said: "The bouncer who knew the man turned him back. The man came back with a heavy-calibre gun, possible a Kalashnikov, and started shooting."
Two of the five people wounded were seriously hurt.
Lille Mayor Martine Aubry said: "Everything must be done to arrest this shooter as quickly as possible so he can face justice."
The March killings in the south-western city of Toulouse and gang murders in the Mediterranean port of Marseille drew attention to the easy availability of illegal weapons in France and their growing use in crime.
The government says there are 7.5 million guns legally owned by the state, gun enthusiasts and hunters.
Nobody knows how many illegal guns are in circulation, though experts put the total number of both legal and illegal guns at between 10 and 20 million in a nation of 65 million people.
Gun laws were tightened in March, before the Toulouse shootings, with the approval of longer jail terms and larger fines for anyone caught with an illegal firearm.