This paper describes the flow and heat transfer characteristics of the mixed convection in a horizontal square duct with density inverse of water by the three-dimensional numerical analysis. The SIMPLE procedure and QUICK scheme were used to solve numerically the governing equations in three-dimensional system through a control volume method. To consider the temperature dependence of fluid properties, they were approximated by the polynomial of the temperature. Numerical results were compared with heat transfer and flow without density inverse. The spiral flow was generated along the flow direction and the starting position of spiral flow moved downward with density inverse. Two recirculation flows were generated near the bottom of side-walls across the section and its size grew up along the flow direction. The maximum intensity of the secondary flow across the section became less than that without the density inverse. Local Nusselt number on the bottom wall increased. However, average Nusselt number on the whole walls decreased.