Objective To optimize the design of three-dimensional (3D) printed scoliosis orthosis with computer-aided design (CAD), so as to achieve the advantages of good mechanical strength and lightweight model. Methods The body contour of a volunteer was scanned by a hand-held 3D scanner, then the body surface model of the volunteer was established. According to the three-point bending principles, traction and load-free principle, the body surface model was modified, and the pressure area and release area were designed. The model of scoliosis orthosis was then designed preliminarily. Comparative study on local optimization of hollow combinations with 32 different sizes were conducted using orthogonal experimental method. According to the optimization results, the model of scoliosis orthosis was hollowed out and biomechanically analyzed. The stress distributions of the 3D printed hollow scoliosis orthosis were compared, and its optimization effect was verified. Results By adopting the optimal design of local hollowing-out with 9 mm-radius and 23 mm-spacing circular hole (40% local weight loss), the 3D printed scoliosis orthosis with lighter weight, better air permeability and sufficient strength could be obtained. Conclusions Based on finite element biomechanical analysis, by adopting local hollow optimization design of circular hole at non-stress area, the 3D printed scoliosis orthosis can achieve the advantages of less printing materials and increased air permeability, and ultimately improve the wearing comfort and compliance of patients.