To explore the clinical effect of itraconazole January oral combined with butenafine hydrochloride cream in the treatment of hyperkeratotic tinea of feet and hands. Methods A total of 80 patients with hyperkeratotic tinea of feet and hands admitted to the Department of Dermatology of our hospital from January 2022 to January 2023 were selected as the research objects. According to different treatment methods, they were divided into control group and study group, with 40 patients in each group. The control group was treated with butenafine hydrochloride cream for external use, and the study group was treated with oral itraconazole capsule combined with butenafine hydrochloride cream for external use. The clinical efficacy, adverse reactions and recurrence were compared between the two groups. Results The total effective rate of treatment in the study group was 95.00%, which was higher than 60.00% in the control group, and the difference was statistically significant (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). The recurrence rates of the study group at 1, 3 and 6 months after treatment were lower than those of the control group, and the differences were statistically significant (P <0.05). Conclusion Itraconazole oral combined with butenafine hydrochloride cream for external use in the treatment of hyperkeratotic tinea of feet and hands has a good clinical effect, which can effectively improve the clinical symptoms of patients, reduce the recurrence rate, and will not increase the risk of adverse reactions.