Objective To observe the efficacy terbinafine hydrochloride and itraconazole in the treatment of onychomycosis. Methods A total of 210 patients with onychomycosis admitted to our hospital from January to December 2021 were randomly divided into study group (n=106) and control group (n=104). The study group took terbinafine hydrochloride tablets orally, and the control group took itraconazole orally. The fungal clearance and adverse reactions were compared between the two groups. Results The effective rate of nail onychomycosis treatment in the study group was 84.44 %, and the effective rate of toenail onychomycosis treatment was 80.33%. The effective rate of nail onychomycosis treatment in the control group was 80.95 %, and the effective rate of toenail onychomycosis treatment was 79.03%. However, there was no significant difference in the total effective rate between the two groups (P>0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The efficacy of terbinafine hydrochloride and itraconazole in the treatment of onychomycosis is similar, they can treat onychomycosis without increasing adverse reactions and have high safety.