To evaluate the therapeutic efficacy and clinical characteristics of ShiShi manipulation in treating knee osteoarthritis. A randomized, controlled trail was performed, 60 patients were randomized into 2 groups to receive either (l)group A, ShiShi manipulation was adopted(N=30), or (2) group B, glucosamine hydrochloride (PuLi capsule) was given to take medicine orally(N=30). Courses of treatment in each group were 4 weeks without exception, follow-up review was arranged every two weeks. WOMAC index was adopted to evaluate general curative efficacy, total scale, pain scale, stiff scale, function scale at 2 weeks and 4 weeks of treatment. Compared with before treatment, group A showed a statistical difference in total scale at 2 weeks and 4 weeks follow-up, while group B showed a statistical difference at 4 weeks follow-up. General curative efficacy, pain scale, function scale in group A were significantly better than group B at 2 weeks and 4 weeks follow-up(P <;0.05), while stiffness scale was similar. ShiShi manipulation can obviously alleviate the clinical symptoms of knee osteoarthritis. also it shows better and rapid therapeutic efficacy than PuLi capsule. We assume that ShiShi manipulations worthy of widely applied in treatment of knee osteoarthritis as a complementary medicine.