In order to investigate the influence of parameter variation and three-dimensional effect on the interaction between conical shock wave and plate boundary layer, Menter-SST two-equation turbulence model is used to simulate the interaction between three-dimensional conical shock wave and plate boundary layer in a supersonic Mach 2 flow, and the results are analyzed qualitatively and quantitatively. The influence caused by the change of shock-wave generator’s half-cone angle and Reynolds number on the flow in the interference region is studied, and the variation rules of flow separation caused by parameter variation are summarized. Moreover, the two-dimensional cases which are equivalent to the incident shock wave on the central symmetry plane in corresponding three-dimensional cases are also calculated, and the results are compared with the three-dimensional cases. The comparison shows that the interference between conical shock wave and plate boundary layer is obviously different from that of two-dimensional cases in terms of wall pressure coefficient, separation vortex, vorticity distribution and so on.