Objective To observe the effect of secukinumab in the treatment of moderate to severe plaque psoriasis. Methods A total of 120 patients with moderate to severe plaque psoriasis admitted to the Department of Dermatology, Shouguang Skin Disease Prevention and Treatment Station from June 2021 to December 2023 were randomly divided into control group and study group, with 60 patients in each group. The control group was treated with calcipotriol ointment for external use, and the study group was treated with secukinumab injection on the basis of the control group. The psoriasis area and severity index (PASI) score, clinical efficacy and adverse reactions were compared between the two groups. Results The PASI score of the two groups after treatment was lower than that before treatment, and the study group was lower than the control group (P <0.05). The total effective rate of treatment in the study group was 96.67%, which was higher than 71.67% in the control group (P <0.05). The incidence of adverse reactions in the study group was 3.33%, which was lower than 16.67% in the control group (P <0.05). Conclusion The external application of calcipotriol ointment combined with secukinumab injection is effective in the treatment of moderate to severe plaque psoriasis, which can effectively improve the symptoms of psoriasis and reduce the degree of skin lesions. Meanwhile, the incidence of adverse reactions after treatment is low and the application safety is high.