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Basal cell carcinoma (BCC) is the most common cutaneous cancer. We report the efficacy and aesthetic outcome of intralesional IFN-α 2b injection for the treatment of BCC and compare with the surgical method. Intralesional IFN-α 2b was injected in 58 BCC lesions from 20 patients three times a week for three weeks. Control group was retrospectively selected among patients who underwent surgical method (standard surgical excision) for BCC including 58 lesions from 24 patients. All patients were followed up for one year in terms of recurrence and cosmetic outcome. Two patients (four lesions) failed to complete the treatment period. After three weeks, 40 (68.96%) lesions were completely cured. Nine (15.51%) lesions achieved complete healing in less than 9 sessions. Five (8.62%) lesions were completely cured by an extra week of injection. In aggregate, complete healing was observed in 54 (93.10%) lesions. In the surgery group, complete lesion elimination was detected in 52 (89.65%) lesions (p = 0.40). After one year, cosmetic outcome was significantly more favorable in the study group compared to the surgery group (p = 0.003). Recurrence was not detected in any of the groups after one year follow-up. Intralesional IFN-α 2b injection is an appropriate treatment choice for BCC. We used Iranian registery of Clinical trials; The IRCT code is: 2017093017756N30 [ABSTRACT FROM AUTHOR]