Objective To observe the relationship between expression of retinoic acid receptor-β (RAR-β) in esophageal squamous cell carcinoma (ESCC) and chemotherapy response. Methods Fifty-two cases advanced ESCC patients treated by DDP and 5-FU, DDP 80 mg/m2, divided into 5 days;5-FU 375 mg/m2, dl-5. Immunohistochemistry was used to exmine the expression of RAR-β in ESCC. Fifty cases normal esophageal tissue were used as controls. Results RAR-β immunoreactivity was recognizd in both cytoplasm and nucleus, RAR-β positive rate was lower in ESCC compared with normal tissue (61.5%vs 92% ,P ＜0. 05 ). The 52 cases ESCC patients were treated 228 chemotherapy cycles, the overall response rate (OR) was 71.2%. The OR in RAR-β positive patients was 84. 4% (27/32), significant higher than RAR-β negative patients 50. 0% ( 10/20 ) ( P ＜ 0. 05 ). The time-to-progression ( TTP ) for RAR-β positive patients was 5.9 months, the median survival period was 12. 1 months, 2 years survival rate was 56. 7%;whereas TTP for RAR-β negative patients was 2. 1 months, the median survival period was 5.8 months,2 years survival rate was 32. 9%. There was signifcant difference between the 2 groups ( P ＜ 0. 05 ) .Conclusion RAR-β protein expression by immunohistochemistry may be a useful indicator to predict the chemotherapy response and clinical outcome for ESCC, meanwhile it may be an avenue for target therapy.