Abstract：Objective：To observe the clinical effect of needle knife for knee osteoarthritis(KOA). Methods：A total of 78 cases of KOA patients were divided into the experiment group and the control group according to the random number table method，39 cases in each group. The experiment group was treated with needle knife，and the control group was treated with acupuncture. Both groups were treated for four weeks. The clinical effect and the scores of Visual Analogue Scale(VAS) in the two groups were compared； the levels of hyaluronic acid(HA)， interleukin- 1β(IL- 1β)， interleukin- 6(IL- 6) and tumor necrosis factor-α(TNF-α) in serum and synovial fluid in the two groups were detected. Results：After treatment，VAS scores in the two groups when staying still，walking and climbing stairs respectively were all decreased when compared with those before treatment(P＜0.05)；VAS scores in the experiment group when walking and climbing stairs were lower than those in the control group(P＜0.05)；the comparison of VAS scores when staying still between the two groups showed no significance difference(P＞0.05). The total effective rate was 97.4% in the experiment group and 79.5% in the control group， the difference being significant(P＜0.05). After treatment，the levels of HA，IL-1β，IL-6 and TNF-α in serum in the two groups were significantly decreased(P＜0.05)；the level of HA in serum in the experiment group was lower than that in the control group(P＜0.05)； there was no significant difference being found in the comparisons of IL- 1β， IL- 6 and TNF- α in serum between the two groups(P＞0.05). After treatment， the levels of HA in synovial fluid in the two groups were significantly increased(P＜0.05)， the level of HA in synovial fluid in the experiment group was higher than that in the control group(P＜ 0.05)；the levels of IL- 1β，IL- 6 and TNF- α in synovial fluid in the two groups were significantly decreased(P＜0.05)，the above three indexes in the experiment group were lower than that in the control group(P＜0.05). Conclusion：The application of needle knife has better clinical effect in treating KOA than that of acupuncture， and can relieve pain more effectively， whose possible mechanism may be making a difference by ragulating the levels of HA，IL-1β，IL-6 and TNF-α in serum and synovial fluid.