Objective To research the effect and safety of sodium hyaluronate and xianlinggubao alone and in combination for the patients with knee osteoarthritis. Methods During the time of October 2014 to October 2016， 90 patients with knee osteoarthritis were selected and divided into A， B and C groups with the principle of voluntary and randomly assignment. The 30 patients ingroup A were treated by xianlinggubao only and the 30 patients ingroup B were treated by sodium hyaluronate only， while the 30 patients in group C were treated by sodium hyaluronate and xianlinggubao. To observe the WOMAC scores and adverse events of the 3 groups. Results The WOMAC score in group C was 17.31±6.90， significantly lower than the that of group A and group B， which were 30.43±7.07 and 28.25±7.19， and the results above were statistically significance while P<0.05. From the view of adverse reactions， there were no patients appeared adverse reaction in group C. Conclusion Sodium hyaluronate and xianlinggubao alone and in combination all can treated knee osteoarthritis， but compared with using xianlinggubao and sodium hyaluronate alone. It can effectively improve the clinical efficacy to use them in combination which can also cut down the adverse reactions and deserved to be used in clinical.