Sheep is a significant agricultural animal and food source for people worldwide. The fat tail/rump is considered as an adaptive selection under harsh challenges which serves as a fat store for the animal. Thyroid hormone responsive (THRSP) is a crucial protein for cellular de novo lipogenesis. THRSP gene encodes a nuclear protein which regulates fatty acid synthesis in lipogenic tissues. Identification of single nucleotide polymorphisms (SNPs) of sheep THRSP gene and their association with fat deposition were investigated using Altay and White Suffolk sheep. In addition, the messenger RNA expression profiling of THRSP in fat-tailed and thin-tailed breeds was compared among 8 different tissues. Four SNPs have been detected in position g. 205A>C, c. 52C>T, c. 364A>T and c. 1031C>T of THRSP gene. Genotyping method was used to analyze genotypes among Altay sheep (fat-rumped breed) and White Suffolk (thin-tailed breed) by Sequenom MassArray. In the c.1031C>T locus, the frequency of T allele of fat-tail breed was significantly (p<0.001) higher than that of the thin-tailed breed using F test, which suggest that this locus may be associated with fat deposition in fat-tail breed. Gene expression levels in both subcutaneous adipose and tail fat tissues were significantly (p<0.01) higher than the other tissues analyzed. Levels of THRSP expression in liver, subcutaneous adipose and tail fat tissues in Tan sheep (thin-tailed breed) were significantly (p<0.01) higher than that in Altay sheep (fat-tailed breed). The results obtained might expand our understanding of the important regulating role of THRSP gene in lipogenesis in fat-tailed sheep breed.