To determine of the expression of Toll-like receptor (TLR) 2, TLR4, TLR7 and TLR8 in Oral squamous cell carcinoma (OSCC). Reverse transcription-polymerase chain reaction and Flow cytometry were used to analyze the expression of TLR2, TLR4, TLR7 and TLR8 mRNA and protein in samples from 50 cancer patients consisting of both tumor and normal tissue. This study was done in Tabriz medical University between 2011 till 2013. A significant increase in TLR2, TLR4, TLR7 and TLR8 mRNA levels was detected in OSCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR2, TLR4, TLR7 and TLR8, respectively, P < 0.05). Nevertheless, a significant percentage of tumors also exhibited TLR4 expression in mononuclear inflammatory cells (48.3%).Tumors with high TLR2 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 TLR8 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR2, TLR4, TLR7 and TLR8 among different ethnic groups. TLR2, TLR4, TLR7 and TLR8 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for OSCC.