p130cas (p130 Crk-associated substrate) is a scaffolding protein and plays an important role in regulating focal adhesion and driving cell migration. Also, the destruction of E-cadherin/β-catenin adhesive complex is one of the changes that characterizes the invasive phenotype of tumors. The aim of this study is to evaluate the role of p130cas, E-cadherin, and β-catenin expression in patients with non-small cell lung cancer (NSCLC). We examined the expression of p130cas, E-cadherin, and β-catenin in 105 lung cancer tissues and paired adjacent normal lung tissues using immunohistochemistry. The overexpression of p130cas was observed in 61.9% (65/105) of lung cancer samples. The overexpression of p130cas was correlated with abnormal expression of E-cadherin and β-catenin (P=0.002 and P=0.006, respectively). Chi-square test showed that the overexpression of p130cas correlated positively with lymph node metastasis and high TNM stage. The Log-Rank test revealed that the mean survival time of patients with p130cas overexpression (36.31 ± 5.66 months) was markedly shorter than those with p130cas normal expression (60.57 ± 6.95 months). Multivariable analysis indicated p130cas overexpression (P<0.001) as an independent significant prognostic factor for NSCLC patients' survival. These results indicate that p130cas may impact a variety of clinicopathological features of NSCLC and may y influence the prognosis of lung cancer patients.