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Previously, we used the ischemia-reperfusion hepatectomy mouse model to show that in the 50% model, the 7-day survival rate of mice was 100%, while in the 85% model was only 20 %. Now, we use bioinformatics analysis to evaluate molecular events. Male C57BL/6J mice (n=21) were divided into 7 groups (n = 3 per group): a sham group, after 20 minutes of ischemia-reperfusion, a 50% and an 85% partial hepatectomy group(three time point). A total of 5313 DEGs were found in the liver of mice by comparison between groups. The application of weighted gene co-expression network analysis identified candidate hub genes and allowed the construction of a free-scale gene co-expression network. Three gene expression modules were significantly related to the 85% hepatectomy group and were referred to herein as the blue， turquoise，yellow module. Analysis also identified three key genes: Fam175b, OGT, and Pde3b.Data showed that apoptosis was a key process in mice 6 hours after liver regeneration; however, between 12 and 24 hours, fat metabolism was the dominant process. The key genes identified in this study may help to provide a new basis for the future treatment of ischemia-reperfusion and partial hepatectomy injury.