Objective：This study aims to investigate the mechanism of lansoprazole on skin inflammation through in vivo and in vitro experiments. Methods：In vivo experiment，mice were given continuous gavage for 6 months. The skin tissue damage of mice was evaluated and analyzed by hematoxylin-eosin staining（HE staining）and immunohistochemistry（IHC）. In vitro experiment，CCK-8 was used to determine the changes of HaCaT cell viability after incubation with 10-200 μmol/L lansoprazole for 24 h and 48 h. After incubation with 10 μmol/L，20 μmol/L and 40 μmol/L lansoprazole for 24 h and 48 h，respectively，the phosphorylation levels of NF-κB in HaCaT cells and the protein expressions of interleukin（IL）-6 and IL-1β in HaCaT cells were detected by Western blot. In addition，the protein expressions of P-p65，IL-6 and IL-1β in HaCaT cells were detected after 24 h and 48 h incubation of HaCaT cells with pyrrolidine dithiocarbamate，an inhibitor of NF-κB signaling pathway，alone or in combination with lansoprazole. Results：In vivo experiment showed that lansoprazole can cause skin damage in mice. In vitro studies found that lansoprazole can decrease cell viability，increase the expression of P-p65 proteins，mediate the activation of the pathway，and further stimulate the expression of inflammatory cytokines IL-6 and IL-1β. PDTC can inhibit the lansoprazole-mediated activation of NF-κB pathway and reduce the expression of inflammatory factors. Conclusion：Lansoprazole can promote the expression of inflammatory factors and induce skin injury，and the mechanism may be related to the activation of NF-κB signaling pathway.