Toll-like receptors (TLRs) play a pivotal role in an innate immunity system, which controls inflammation responses and further instructs development of adaptive immunity. We enrolled 250 Han Chinese in Taiwan screening for the single nucleotide polymorphisms (SNPs) in TLRs associated with viral infection, including TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9. The 6 SNPs not hitherto identified in Chinese populations, including TLR3 1377 C>T, TLR3 -7 C>A, TLR7 Gln11Leu, TLR7 IVS1+1817 G>T, TLR8 Met1Val, and TLR8 -129 G>C, had minor allele frequencies of 38%, 23%, 22.3%, 3%, 16.0%, and 16.0%, respectively. The frequencies of 2 common SNPs, TLR9, -1486 T>C and 2848 G>A, were 28% and 44%, respectively. As compared with other ethnic populations, Chinese displayed an opposite allele frequency of TLR8 Met1Val and TLR8 -129 G>C to Caucasians and African Americans. In addition, TLR2 Arg677Try, TLR2 Arg753Gln, TLR4 Asp299Gly, and TLR4 Thr399Ile that were apparent in approximately 10% of Caucasians were not detected in Chinese. In conclusion, obvious ethnic differences in TLR polymorphisms may in part reflect the ethnic diversity of host viral susceptibility.