Objective To analyze the clinical effect and safety of naftifine hydrochloride and ketoconazole cream in the treatment of tinea corporis-cruris and tinea manus-pedis. Methods A total of 187 patients with tinea corporis-cruris and tinea manus-pedis admitted to the Department of Dermatology, Hospital of Traditional Chinese Medicine of Emeishan City from January to December 2020 were selected as the study subjects. They were divided into control group (94 cases) and observation group (93 cases) by random number table method. The control group was treated with miconazole nitrate cream, and the observation group was treated with naftifine hydrochloride and ketoconazole cream. The therapeutic effect, incidence of adverse reactions, recurrence rate and quality of life improvement of the two groups were compared. Results The total effective rate of the control group was lower than that of the observation group, and the difference was statistically significant (P＜0.05). The incidence of adverse reactions in the control group was higher than that in the observation group, and the difference was statistically significant (P＜0.05). The recurrence rate of the control group was 13.83%, which was higher than 3.23% of the observation group, and the difference was statistically significant (P＜0.05). The GQOLI-74 scores of the two groups were higher than those before treatment, and the observation group was higher than the control group, the difference was statistically significant (P＜0.05)；he satisfaction of the observation group was higher than that of the control group, and the difference was statistically significant (P＜0.05)Conclusion Naftifine hydrochloride and ketoconazole cream is effective in the treatment of tinea corporis-cruris and tinea manus-pedis, which can reduce the incidence of adverse reactions, reduce the recurrence rate and improve the quality of life of patients.