Due to the merits of high rigidity and good dynamics, hybrid machine tools have been gradually applied to efficient machining of thin-walled workpiece with complex geometries. However, the discontinuity of tangential component of toolpath in hybrid machine tools may cause velocity fluctuations, leading to poor surface quality of workpiece. In this paper, a novel 5-axis hybrid machine tool is taken as an example to demonstrate a smooth toolpath interpolation method. First, an adaptive acceleration and deceleration control algorithm is presented to realize the smooth transition between two constrained velocity points. Second, a spline curve-based interpolation algorithm is proposed to realize the smoothness of the trajectory. Meanwhile, a parameter synchronization method is proposed to ensure the synchronization of the interpolated tool-axis vector and the interpolated tool tip. Thirdly, an inverse kinematic analysis is conducted based on an inverse position solution model and a velocity mapping model. Finally, a set of machining tests on S-shape workpiece in line with the ISO standard is carried out to verify the effectiveness of the proposed smooth toolpath interpolation method.