AIM: To investigate the expression of Toll-like receptor (TLR) 3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma (ESCC). METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression of TLR3, TLR4, TLR7 and TLR9 mRNA and protein in samples from 87 esophageal cancer patients consisting of both tumor and normal tissue. RESULTS: A significant increase in TLR3, TLR4, TLR7 and TLR9 mRNA levels was detected in ESCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR3, TLR4, TLR7 and TLR9, respectively, P < 0.05). Nevertheless, a significant percentage of tumors also exhibited TLR4 expression in mononuclear inflammatory cells (48.3%) and TLR9 expression in fibroblast-like cells (60.9%). Tumors with high TLR3 expression in tumor cells or high TLR4 expression in mononuclear inflammatory cells were significantly associated with a higher probability of lymph node metastasis and increased depth of invasion. However, tumors with high TLR9 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR3, TLR4, TLR7 and TLR9 among different ethnic groups. CONCLUSION: TLR3, TLR4, TLR7 and TLR9 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for ESCC. AIM: To investigate the expression of Toll-like receptor (TLR) 3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma (ESCC). METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression of TLR3, TLR4 , TLR7 and TLR9 mRNA and protein in samples consisting of both tumor and normal tissue. RESULTS: A significant increase in TLR3, TLR4, TLR7 and TLR9 mRNA levels were detected in ESCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR3, TLR4, TLR7 and TLR9, respectively, P <0.05). A significant percentage of tumors also showed TLR4 expression in mononuclear inflammatory cells in fibroblast-like cells (60.9%). Tumors with high TLR3 expression in tumor cells or high TLR4 expression in mononuclear inflammatory cells were significantly associated with a higher probability of lymph node metastasis and increased d However, tumors with high TLR9 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR3, TLR4, TLR7 and TLR9 among different ethnic groups. CONCLUSION: TLR3 , TLR4, TLR7 and TLR9 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for ESCC.