We aimed to study the expression status of beta-arrestin1 in non-small cell lung cancer (NSCLC) specimens and its clinicopathologic significance. The correlation between beta-arrestin1 and the tumor migration biomarker E-cadherin, as well as smoking index were studied. A total of 152 patients with NSCLC who undergone surgery were enrolled. Altogether, 88 lung squamous cell lung cancer (SCC) specimens and 64 adenocarcinoma (ADC) specimens were tested for immunohistochemistry. Patients' survival was analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were performed to determine independent prognostic factors. Spearman rank correlation test was used to show data associations. For SCC patients, the expression of beta-arrestin1 was either lost (56 of 88, 63.6 %) or low (32 of 88, 36.4 %), which was significantly and negatively associated with E-cadherin expression (P = 0.017). The similar correlation existed between smoking index and beta-arrestin1 expression (P = 0.044). For ADC patients, the deletion of beta-arrestin1 expression was rare (4 of 64, 6.3 %). Loss of beta-arrestin1 expression indicated poorer survival for both SCC (P = 0.026) and ADC patients (P = 0.006). beta-arrestin1 expression was detected in the other ADC specimens but showed no significant correlation with survival. In SCC patients, the loss expression of beta-arrestin1 was frequently observed, and beta-arrestin1 expression was significantly correlated with the smoking index and E-cadherin expression, which all indicated beta-arrestin1's significant clinicopathologic role. However, beta-arrestin1 was expressed in most ADC patients, but its clinicopathologic role seemed to be obscure and might need further exploration.