Objective To compare the clinical efficacy of glucosamine hydrochloride and Chinese traditional medicine of angelicae pubescentis and loranthi decoction in the treatment of knee osteoarthritis. Methods We included 142 patients with mild-to-moderate knee osteoarthritis treated between January 2014 and July 2015. The patients were randomly divided into treatment group and control group. The 72 patients in the treatment group received glucosamine hydrochloride, while the other 70 patients in the control group took oral Chinese medicine of angelicae pubescentis and loranthi decoction. The treatment course was one month. We observed the clinical curative effect of both the two groups. Results After the treatment, the difference in Visual Analogy Score (VAS) and Severity Index of Osteoarthritis (ISOA) in the two groups were significant compared with those before the treatment (P ＜ 0.05) . There were significant differences between the two groups in terms of VAS pain score, ISOA and treatment effectiveness (P ＜ 0.05) . Conclusion Glucosamine hydrochloride can obviously relieve knee osteoarthritis symptoms and improve knee function, which has a better curative effect than the traditional Chinese medicine of angelicae pubescentis and loranthi decoction.