Abstract: Objective To evaluate the effect of intra-articular injection of hyaluronateacid combined with drugs and functional exercise on early and middle-stage knee osteoarthritis (KOA). Methods Fifty-four patients diagnosed as KOA from September 2015 to January 2018 were randomly divided into hyaluronateacid group and control group. The control group received oral glucosamine sulfate (50 mg, 3/d) and routine exercise for 3 months. Hyaluronateacid group received intra-articular injection of hyaluronate acid(4 ml, 1/week) for 4 times on the basis of treatment for control group. Modified WOMAC (Western Ontario and McMaster Universities osteoar thritis index) score was collected at 3 and 6 months to evaluate the treatment effect. Results There was no statistical difference in baseline data between the two groups. The WOMAC score in the hyaluronateacid group and the control group were 36.15±10.56 vs 34.00±11.23 (P=0.54) at 3 months, and 30.15±11.30 vs 26.50±12.43 (P=0.34) at 6 months, without significant difference. Conclusion The combination of oral medication, exercise and intra-articular injection of hyaluronate acid is not superior to oral medication combined with exercise for KOA. We do not recommend intra-articular hyaluronateacid as standard treatment for KOA patients.