OBJECTIVE To observe clinical effects of platelet-rich plasma (PRP) intra-articular and extra-articular injection for patients with knee osteoarthritis (KOA), and analyze its safety and clinical efficacy. METHODS From January to December 2017, 48 patients with KOA were randomly divided into observation group and control group, 24 cases in each group. The observation group was treated with intra-articular injection of PRP (2 ml) and extra-articular injection of PRP (2 ml), once a week, for three times, including 8 males and 16 females with an average of (58.04±7.87) years old ranging from 43 to 68 years old, the courses of disease ranged from 1 to 8 years with an average of (4.69±1.96) years, the body mass index (BMI) was (24.53±5.26) kg/m 2 . The control group was treated with intra-articular injection of sodium hyaluronate (20 mg), extra-articular injection of analgesic drug (2 ml for one point), once a week, for three times, including 7 males and 17 females with an average of (60.54±8.93) years old ranging from 47 to 72 years old, the courses of disease ranged from 1.5 to 9 years with an average of (5.27±1.68) years, BMI was (23.47±4.62) kg/m 2 . VAS score and Lysholm score before operation and the 1st, 6th month after treatment were compared between two groups. RESULTS All patients were followed up at least 6 months without occurrence serious adverse reactions or complications. VAS score in observation group and control group before treatment and 1st, 6th month after treatment were 7.35±1.47, 4.15±1.52, 2.26±1.02 and 7.51±1.39, 3.84±1.76, 3.66±1.18, respectively; VAS score in obsevation group was lower than that of control group at 6 months after treatment. Lysholm score in observation group and control group before treatment and 1st, 6th month after treatment were 55.21±5.78, 79.16±7.25, 85.45±6.87 and 54.65± 6.40, 77.58±6.94, 82.34±7.12. There were significant differences in Lysholm score before and after injection between two groups (P<0.05) . There was no significant difference in Lysholm score between two groups at 1 month after treatment (P>0.05), while Lysholm score in observation group was better than that of control group at 6 months after treatment (P<0.05) . CONCLUSIONS Intra-articular and extra-articular injection of PRP could relieve pain symptoms and improve function of knee joint with higher safety, although the short-term effect is not significantly different from traditional treatment, its medium-long-term effect is stable. It is a safe and effective method for the treatment of knee osteoarthritis.