The study was aimed to observe mir-210 expression in liver tissue of acute cold stress rat and predict the function of mir-210 in cold stress. Thirty SPF Wistar male rats which were 12-week-old and weighed (340 ± 20) g were used. The rats were pre-fed in normal room temperature for one week, and then were randomly divided into acute cold stress group at (4 ± 0.1) °C and normal control group at (24 ± 0.1) °C. After the rats were treated with cold stress for 12 h, the liver tissue was extracted and the gene expression of mir-210 was assayed using qRT-PCR. The results demonstrated that the gene expression of mir-210 was significantly enhanced in acute cold stress group compared with that in normal control group (n = 3, P < 0.01). The bioinformatics analysis showed that mir-210 has over hundreds of target genes and four kinds of target genes such as E2F3, RAD52, ISCU and Ephrin-A3 are more relative with liver cold stress. ISCU regulates the cell respiratory metabolism and Ephrin-A3 is related with cell proliferation and apoptosis. On the other hand, up-regulated mir-210 affects the DNA repairing mechanism which usually leads to genetic instabilities. Our results suggest that cold stress-induced up-regulation of mir-210 in liver harmfully influences cell growth, energy metabolism and hereditary.