Objective To investigate the changes of differentially expressed genes before and after in the liver xenotransplantation, and they were screened and verified. Methods Four cases of xenograft splenic fossa heterotopic auxiliary liver transplantation were performed with a -1，3- galactoside transferase gene knockout（GTKO） mini-pig as donor and Tibetan macaque as recipient. Appropriate preoperative liver specimens were harvested from the donor liver at the back table procedure，and postoperative liver specimens were harvested by biopsy at 48 h afteropening the blood flow of the graft. High throughput chip analysis of miRNAs and mRNAs was performed on the transplanted liver specimens. The key differential expression of miRNAs and mRNAs were screened，and real-time quantitative PCR and Western Blot tests were performed. Results There were 165 miRNAs differentially expressed after surgery，and 112 of them were up-regulated and 53 were down-regulated. Twelve differentially expressed miRNAs，such as mi-23b，were screened and verified. In addition to miR-150 and miR-126-3p，the expression changes of other miRNAs were basically consistent with the results of miRNAs chip. Compared with preoperative data，2 035 mRNAs showed significant differential expression after operation，922 of them were up-regulated and 1 113 were down-regulated，5 differentially expressed genes which were closely related to liver transplantation, such as IGFBP6，CDK2AP1，TNFAIP6，FⅦ and NKG2D，were screened at mRNA and protein levels. Except for NKG2D，the changes in the protein level of the other 4 genes were basically consistent with the changes in the mRNA level（P ＜ 0.05），but the changes in the CDK2AP1 protein were small，and there was no statistical difference （P ＝ 0.073）. Conclusion The expression of miRNAs and mRNAs in transplanted liver after xenotransplantation has greatly changed. These differentially expressed genes may be related to immune injury and coagulation dysfunction.