Objective:To investigate the effect of Qianghuo Decoction iontophoresis combined with joint mobilization technique in treating Knee Osteoarthritis (KOA) patients with cold-damp syndrome. Methods:A total of 98 KOA patients, who were admitted in our hospital from October 2017 to October 2018, were randomly divided into control group and observation group (49 in each group) according to random number table method. Both groups were treated by joint mobilization technique. The control group were given Glucosamine sulfate capsule (0.5 g/time and tid) orally. The observation group was treated by iontophoresis of Qianghuo Decoction. After 6 weeks’ treatment, to evaluate syndrome of cold-damp, the efficacy, by using bone metabolism indexes, the Western Ontario and McMaster Universities (WOMAC) and symptoms of such as serum levels of collagen type Ⅱ C-peptide (CTX-Ⅱ), collagen type Ⅰ C-peptide (CTX-Ⅰ), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and the pain medium indexes, such as serum levels of prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT) were compared between two groups. Results:After the treatment, the total efficacy in the observation group was 93.9% (46/49), the control group was 77.6% (38/49), and the difference between the two groups was statistically significant ( χ2=4.083, P=0.043). After the treatment, scores of WOMAC indexes joint pain, joint stiffness, limited daily movement of the observation group were significantly lower than those of the control group ( t values 8.430, 9.986, 12.776, respectively, all Ps<0.01), and scores of symptoms joint pain, joint temperature pain reduction, morning stiffness, waist pain of the observation group were significantly lower than those of the control group ( t values 8.825, 9.043, 7.230, 7.034, respectively, all Ps <0.01). After treatment, the serum levels of CTX-Ⅰ (404.99 ± 43.35 g/L vs. 458.69 ± 48.61 g/L, t=21.005), CTX-Ⅱ (414.99 ± 43.39 g/L vs. 484.06 ± 50.77 g/L, t=18.991), TRACP-5b (2.98 ± 0.35 U/L vs. 5.67 ± 0.61 U/L, t=9.043) of the observation group were significantly lower than those of the control group ( P<0.01); while the serum levels of PGE2 (167.81 ± 18.79 g/L vs. 252.61 ± 27.34 g/L, t=26.389), SP (143.67 ± 15.92 g/L vs. 179.55 ± 19.53 g/L, t=25.416), DA (9.15 ± 1.15 g/L vs. 13.17 ± 1.81 g/L, t=10.445), 5-HT (615.08 ± 63.95 g/L vs. 712.69 ± 72.88 g/L, t=31.004) were significantly lower than those of the control group ( P<0.01). Conclusions:Iontophoresis of Qianghuo Decoction combined with joint mobilization technique for KOA patients with syndrome of cold-damp can improve the symptoms of the patients, reduce the level of bone metabolism, reduce the pain mediators, improve clinical symptoms and enhance efficacy.