In our study, besides discovering that CLDN4 could be a predictive marker for recurrent MPE in advanced NSCLC, we further found that the expression level of CLDN4 was positively correlated with the expression of VEGFA and HIF1A, and also validated that hypoxia‐induced angiogenesis and MIF signalling contributed mostly to the recurrence of MPE. Here, CLDN4 is linked to non-small cell lung carcinoma.