AIB1 (amplified in breast cancer 1) is frequently overexpressed in esophageal squamous cell carcinoma (ESCC), but the significance of AIB1 expression in chemoradiotherapy (CRT) sensitivity and its effect on prognosis are still unclear. In this study, the expression of AIB1 was examined by immunohistochemistry in 98 biopsy specimens of primary ESCC patients treated with definitive CRT. AIB1 overexpression was found in 63/98 (64.3%) of the ESCCs. There was a significant association between AIB1 overexpression and distant lymph node metastases (P = 0.011), but not regional lymph node metastases. In the M0 subgroup, overexpression of AIB1 was observed more frequently in stage T4 than in stage T2-3 (66.7%vs 38.5%, P = 0.031). In addition, AIB1 expression was the only factor that showed a significant correlation with CRT response, in which overexpression of AIB1 was observed more frequently in the CRT resistant group than in the CRT effective group (86.5%vs 50.8%, P < 0.001). Univariate analysis revealed that AIB1 overexpression was associated with poor progression-free survival (PFS) (P < 0.001) and poor disease-specific survival (DSS) (P <0.001). Furthermore, AIB1 expression could stratify patient survival in stages T2-3, T4, N1, and M0 (P < 0.05), as well as in the CRT effective group (P < 0.05), and AIB1 overexpression and CRT resistance were evaluated as significant independent prognostic factors for both PFS and DSS in multivariate analysis. These findings suggest that overexpression of AIB1 is a useful predictor of CRT resistance and an independent molecular marker of poor prognosis for ESCC patients.