It will be the third time the two sides have met, the first time back in 2001 and also played at the Stoop in February 2002.
The Sharks have won both previous matches so Quins will be looking for third time lucky against the Super 12 side.
Mark Evans, CEO of NEC Harlequins said: "We are delighted that our friends at the Sharks will be making the trip to the Stoop again. The previous games here have been magnificent entertainment in front of packed houses and I'm sure this season's contest will be just as exciting and enjoyable."
Tickets are available from Monday, October 6 by calling the Quins Ticketline on 0871 871 8877.
The London club are once again expecting a capacity crowd at the fixture, but those supporters unable to get a ticket will be able to watch the game live and exclusive on Sky Sports.