Objective To analyze the effect of secukinumab injection on skin barrier function indexes in patients with moderate to severe plaque psoriasis. Methods A total of 50 patients with moderate to severe plaque psoriasis admitted to our hospital from January 2023 to June 2024 were selected as the research subjects. According to the random number table method, they were divided into the reference group (n =25) and the study group (n =25). The reference group was treated with calcipotriol ointment combined with acitretin capsules, and the study group was treated with secukinumab injection on the basis of the reference group. The clinical efficacy, skin barrier function indexes, Psoriasis Area and Severity Index (PASI) score, Vascular Endothelial Growth Factor (VEGF) level and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the study group was 92.00%, which was higher than 72.00% in the reference group (P <0.05). After treatment, the stratum corneum hydration and oil content in the two groups were higher than those before treatment, and those in the study group were higher than those in the reference group (P <0.05). After treatment, the PASI score in the two groups was lower than that before treatment, and that in the study group was lower than that in the reference group (P <0.05). After treatment, the VEGF level in the two groups was lower than that before treatme nt, and that in the study group was lower than that in the reference group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion The application effect of secukinumab injection in the treatment of moderate to severe plaque psoriasis is good, which can repair the skin barrier function, alleviate the symptoms of psoriasis, and does not increase the probability of adverse reactions. It is a safe and effective treatment option.