BACKGROUND: TRIM29 belongs to the tripartite motif (TRIM) protein family. It has been reported to be up-regulated or be down-regulated in many cancer types, suggesting the oncogenic function of TRIM29 may be depend on different molecular signaling pathway. It was found that ß-catenin function (a key molecule in the Wnt signaling pathway) was required for TRIM29's oncogenic effects. TRIM29 gene expression was also found to be heterogeneous in non-small-cell lung cancer (NSCLC) subtypes. In this study, the possible associations of TRIM29 expression with clinicopathological factors, prognosis, and ß-catenin in human NSCLC were analyzed. METHODS: TRIM29 and ß-catenin expression of tumor and adjacent normal tissues in 251 cases of NSCLC treated by surgery was detected by the Immunohistochemical method. The relationship between clinical pathological data, ß-catenin, and TRIM29 expression was analyzed. RESULTS: TRIM29 expression of tumor tissues was significantly higher than adjacent normal tissues. Expression of TRIM29 in squamous cell carcinoma (SC) tissues was positively correlated with abnormal expression of ß-catenin, histological grade, tumor-node-metastasis (TNM) stage, and lymph node metastasis and that was positively correlated with tumor size, histological grading, TNM stage and lymph node metastasis in adenocarcinoma (AC). TRIM29 expression in SC and AC was significantly different and the intensity of poorly differentiated SC was significantly higher than that of AC. High-expression of TRIM29, poorly differentiated grade, and high clinical stage were independent prognostic indicators. CONCLUSION: We considered that TRIM29 may play a reference role in distinguish poorly differentiated AC and SC of NSCLC, combining with CK5/6 and CK7, and it could improve postoperative assessment and have the reference value for clinical treatment. The interaction between TRIM29 and ß-catenin may participate in the development of lung SC.