To observe the relationship between expression of retinoic acid receptor-β(RAR-β) in esophageal squamous cell carcinoma (ESCC) and chemotherapy response.Fifty-two cases advanced ESCC patients treated by DDP and 5-FU, DDP 80 mg/m(2), divided into 5 days; 5-FU 375 mg/m(2), d1-5. Immunohistochemistry was used to examine the expression of RAR-β in ESCC. Fifty cases normal esophageal tissue were used as controls.RAR-β immunoreactivity was recognized 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 significant difference between the 2 groups (P < 0.05).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.