Background and purpose:δ-catenin is a member of the p120 catenin subfamily, which can directly bind to E-cadherin on the cell membrane, forming E-cadherin/catenin complex. δ-catenin can also affect the cytoskeleton assembly by regulating the activity of Cdc42 (Small GTPase). Therefore, this study detected the expression of δ-catenin and Cdc42 in non-small cell lung cancer (NSCLC) and investigated the relationship between them.Methods:The expressions of δ-catenin and Cdc42 in 122 cases of NSCLC were detected by immunohistochem-istry. This study also used Western blot and real-time lfuorescent quantitative polymerase chain reaction (RTFQ-PCR) to detect the protein and mRNA expressions of δ-catenin and Cdc42 in lung cancer tissues. After up-regulating or down-regulating δ-catenin in lung cancer cell line, the activity of Cdc42 and invasion ability of lung cancer cells were detect-ed by G-LISA and Transwell.Results:The mRNA and protein expression of δ-catenin and Cdc42 in lung cancer tissues was signiifcantly higher than that in normal lung tissues. In 122 NSCLC cases, the δ-catenin positive expression rate was 65.57% (80/122), and the Cdc42 overexpression rate was 68.03% (83/122). There was a good correlation betweenδ-catenin positive expression and Cdc42 overexpression (P<0.001). The co-expression of δ-catenin and Cdc42 was related to the high clinical stage, poor differentiation, adenocarcinoma and lymph node metastasis of lung cancer (P<0.05), and was signiifcantly associated with poor prognosis in patients with lung cancer. In the lung cancer cell line, the expression and the activity of Cdc42 were changed by regulating the δ-catenin expression, which affected invasion ability of the lung cancer cells.Conclusion:The δ-catenin expression was significantly correlated with the Cdc42 expression. The co-expression of δ-catenin and Cdc42 in lung cancer was correlated with the poor prognosis of lung cancer.