Abstract A real-time path generation method with Non Uniform Rational B Spline(NURBS) technology in the Computer Aided Design(CAD) field is presented and realized in a five-axis Computer Numerically Controlled(CNC) system. In this method, the tool path was represented into two NURBS curves, tooltip and tool-orientation spline curve, based on the same knot vector. The Cutter Location(CL) data was firstly calculated and then transformed to five motion commands of five axes of machine tool through the real-time post-procession algorithm. The acceleration/deceleration controlling method was also presented to avoid the impact of machine tool. The proposed five-axis spline interpolation method is realized in our developing five-axis CNC machine tool and the result of machining shows that the method is feasible.