Abstract：Objective：To observe the clinical effect of tripterygium glycosides tablets combined with halometasone cream for prurigo nodularis(PN). Methods：A total of 82 cases of PN patients were divided into the control group and the observation group according to the random number table method，41 cases in each group. The control group was treated with occlusive wrap with halometasone cream， and the observation group was treated with halometasone cream combined with tripterygium glycosides tablets. After four weeks of treatment， the skin lesions and pruritus of patients were scored， the levels of tumor necrosis factor- α(TNF- α) and substance P(SP) in serum were detected， and the curative effect was evaluated. Results： After treatment， the scores of skin lesions including number of nodules， nodule size， cornerization degree，degree of hypertrophy and exfoliation degree of epidermis，the total scores of skin lesions and the pruritus scores in the two groups were decreased when compared with those before treatment(P＜0.05)；the above indexes in the observation group were lower than those in the control group(P＜0.05). After treatment，the levels of TNF-α and SP in serum in the two groups were decreased when compared with those before treatment(P＜0.05)； the above levels in the observation group were lower than those in the control group(P＜0.05). The total effective rate was 85.37% in the observation group and 65.85% in the control group， the difference being significant(P＜0.05). There were two cases of poor appetite and one case of diarrhea in the observation group， and there was no significant adverse reaction in the control group. Conclusion： Tripterygium glycosides tablets combined with halometasone cream for PN can effectively reduce levels of TNF- α and SP in serum and improve the symptoms of skin lesions and pruritus and the clinical effect.