To investigate the clinical effect of secukinumab injection 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 of Gaotai County Hospital of Traditional Chinese Medicine from March 2020 to March 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 60 patients in each group. The control group was treated with calcipotriol ointment, and the observation group was treated with secukinumab injection. The skin barrier function, symptom severity score, clinical efficacy and adverse reactions were compared between the two groups. Results The sebum content and stratum corneum water content of the two groups after treatment were higher than those before treatment, and the observation group was higher than the control group (P <0.05). The pH value of the two groups after treatment was lower than that before treatment, and that of the observation group was lower than that of the control group (P <0.05). After treatment, the skin lesion area, erythema, infiltration, scale index score and total score of the two groups were lower than those before treatment, and the observation group was lower than the control group (P <0.05). The total effective rate of treatment in the observation group was 98.33%, which was higher than 83.33% in the control group (P <0.05). The incidence of adverse reactions in the observation group was 10.00%, which was slightly higher than 6.67% in the control group, but the difference was not statistically significant (P >0.05). Conclusion Secukinumab injection in the treatment of patients with moderate to severe plaque psoriasis can effectively improve the skin barrier function, relieve clinical symptoms, improve the curative effect, and has high safety, which is worthy of clinical application.