The relationship between TACC3, a member of the transforming acidic coiled-coil proteins (TACCs) family, and lung carcinoma remains unclear. The present study was designed to explore the prognostic and clinical significance of TACC3 in non-small cell lung cancer (NSCLC). An immunohistochemistry (IHC) assay was performed to analyze the expression of TACC3 in 195 lung cancer cases. The mRNA and protein levels of TACC3 were examined by quantitative reverse transcription-PCR or western blotting. The correlation between TACC3 expression and clinicopathological factors was analyzed by χ2 analysis and Fisher's exact test. Kaplan-Meier analysis and the Cox proportional hazards model were used to examine the correlation of prognostic outcomes with TACC3. The results showed that the levels of TACC3 mRNA and total protein were higher in lung cancer lesions than paired non-cancerous tissues. IHC analysis revealed that TACC3 was highly expressed in 94 (48.2%) cases. The expression of TACC3 was strongly correlated with smoking status, histological classification, differentiation, cytokeratin 19 fragment levels, T stage and the clinical stage of NSCLC patients. Univariate and multivariate analyses demonstrated that TACC3 is a useful biomarker for NSCLC prognosis. The low TACC3 expression group exhibited better progression-free survival (PFS) among patients who received anti-microtubule chemotherapy. In conclusion, the results showed that a high level of TACC3 expression was correlated with advanced clinicopathological classifications, poor overall survival (OS) and poor recurrence-free survival (RFS) in NSCLC patients. Our findings indicate that TACC3 is a potential prognostic marker and therapeutic target for NSCLC.