Background: Melasma is a highly prevalent hyperpigmentation disorder with a high relapsing rate and a negative impact on the psychological state of the affected patients. The exact pathogenesis of melasma is not completely elucidated; however, ultraviolet induced oxidative stress has an important role in its pathogenesis. Silymarin, antioxidant drug, reduces the harmful effects of solar ultraviolet radiation such as inflammation, immune responses, DNA damage, and pigmentation. Objectives: To assess the efficacy and safety of topical silymarin with different concentrations (0.7% and 1.4%) versus hydroquinone 4% in the treatment of melasma. Methods: Forty‐two adult female patients with melasma were assigned to three equal groups each containing 14 patients; group1 was treated by silymarin 0.7% cream, group 2 was treated by silymarin 1.4% cream and group 3 was treated by hydroquinone 4% cream. The duration of treatment was 3 months. Results: MASI score was significantly reduced in all groups at the end of third month; however, there were no significant differences in the therapeutic response between the three studied groups. No side effects were recorded with silymarin, while hydroquinone was associated with significant adverse effects. Conclusions: Silymarin cream might serve as an effective and safe treatment modality for melasma.