Objective To evaluate the curative effect of the Duhuo-Jisheng decoction in treating knee osteoarthritis (KOA) with the deficiency of liver and kidney. Methods Using the random number table method, a total of 80 KOA patients were randomly divided into 2 group, 40 in each group. The treatment group were treated with Duhuo-Jisheng decoction, and the control group with glucosamine sulfate orally. The 2 groups were treated with 30 day. The blood sedimentation (ESR) of before and after treatment was detected. The level of C-reactive protein (CRP) was detected by latex enhanced immunization. The degree of knee joint pain was evaluated by VAS scale. The severity of the symptoms was evaluated by the visual scale of Osteoarthritis Index (Western Ontario Mac Master University Osteoarthritis index, WOMAC index). The changes of TCM symptoms were observed and the clinical effective rate was evaluated. Results The total effective rate of the treatment group was 95% (38/40), while the control group was 77.5% (31/40). The difference between the 2 groups was statistically significant (χ2=10.213, P=0.003). After treatment, the ESR (15.41 ± 4.23 mm/h vs. 17.6 ± 7.27 mm/h, t=-4.426), CRP (4.73 ± 1.28 mg/L vs. 6.12 ± 2.38 mg/L, t=-14.735) level in the treatemnt group were significantly lower than those in the control group (P<0.01). The VAS scores (2.5 ± 0.62 vs. 4.9 ± 0.8, t=-15.026), WOMAC index(12.1 ± 4.7 vs. 16.7 ± 6.7, t=-11.177) and TCM symptom score (6.5 ± 0.4 vs. 7.5 ± 0.4, t=-3.482) in the treatment group were significantly lower than those in the control group (P<0.01). Conclusions The Duhuo-Jisheng decoction is effective improve the symptom and quality of life of liver-kidney deficiency of KOA.