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Tunnel fire smoke control is an important issue in the area of tunnel fire safety. Inspired by fire compartmentation in buildings, it is worth investigating whether a tunnel can be partitioned by a water mist system into a fire zone and safety zones. If so, people can move from the fire zone into a safe zone through the water mist system. Obviously, an essential question is to examine to what extent the fire-induced heat and smoke can be blocked by the water mist system. Thus, in present paper, CFD simulations were conducted to investigated the effectiveness of water mist systems on blocking fire-induced heat and smoke in a full-scale tunnel. We mainly focus on the impact of nozzle combination on smoke blocking effect. Simulation results show that the entrainment caused by the water mist system plays the main role on blocking fire-induced smoke, and the nozzle combination has small impact on heat blocking effect. Based on the momentum balance of the water mist system and ceiling jet smoke flow, a correlation of total water flow rate of the water mist system and fire heat release rate was proposed.