Abstract: To simulate three-dimensional flow around complex geometrics, a hybrid method based on Cartesian grid and meshless method is presented. In this hybrid method, the efficient Cartesian grid covers the whole computational domain, while a relatively small domain adjacent to the body surface is covered by meshless points. By implementing domain identification and information communication in the overlapping domain, several computational domains are coupled together, and the complicated computational system is formed. To validate the applicability and accuracy of this hybrid method, the supersonic sphere flow is calculated, and the location and the shape of the shock obtained are compared with the empirical formula data. The B1AC2R generic missile at Ma=2.5 and angles of attack 0°~10° is also simulated, the computational results including the aerodynamic coefficients are in a good agreement with the experimental data. It is found that the hybrid method presented is available for actual engineering problems.