A computational fluid dynamics (CFD) model is presented that couples the fluid dynamics with various processes involving precursor droplets and product particles during the flame spray pyrolysis (FSP) synthesis of silica nanopowder from volatile precursors. The transport and evaporation of liquid droplets are simulated from the Lagrangian viewpoint. The quadrature method of moments (QMOM) is used to solve the population balance equation (PBE) for particles undergoing homogeneous nucleation and Brownian coagulation. The nucleation rate is computed based on the rates of thermal decomposition and oxidation of the precursor with no adjustable parameters. The synthesis of silica nanopowder from tetraethylorthosilicate (TEOS) in a bench-scale FSP reactor was simulated. The computed results show that the model is capable of reproducing the magnitude as well as the variations of the average particle diameter with different experimental conditions using a single value of the collision efficiency factor α.