〔Abstract〕 Objective To investigate the characteristic genes of Programmed cell death protein 1(PD-1) immunotherapy sensitivity in Hepatocellular carcinoma(HCC). Methods The common differential genes in GSE202069 and ERP117672 data sets were investigated by Weighted Gene Co-expression Network Analysis(WGCNA) and Difference analysis, and the characteristic genes of PD-1 immunotherapy sensitivity were screened through Lassoregression. The expression levels of characteristic genes in HCC were predicted by GEPIA and Ualcan databases, and their expression was verified by real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR), Western blot(WB) and Immunohistochemistry(IHC). 3-hydroxybutyrate dehydrogenase 1(BDH1) overexpressed cell line was constructed, followed by cell counting kit-8(CCK-8), EdU, cell scratches and Transwell experiment to investigate the effects ofBDH1on the proliferation, migration and invasion of HCC cells. Results Total of 118 common differentially expressed genes were identified in two datasets by WGCNA and differential analysis. The characteristic genes associated with PD-1 immunotherapy sensitivity screened through Lasso regression including Flavin containing dimethylaniline monoxygenase 3(FMO3), Peroxisomal trans-2-enoyl-CoA reductase(PECR),BDH1, Solute carrier family 7 member 1(SLC7A1), Cytochrome b5 type A(CYB5A) and Phosphoenolpyruvate carboxykinase 1(PCK1). Survival analysis showed thatBDH1was most associated with HCC(Overall survival:P<0.001, Recurrence:P=0.007). GEPIA and Ualcan databases showed low expression ofBDH1in HCC tissues, while RT-qPCR, WB, and IHC further confirmed this. CCK-8, plate cloning assay, EdU staining, cell scratch, and Transwell experiments showed that compared with the Hep3B pCDH group, overexpression ofBDH1resulted in a decrease in the absorbance of HCC cells(t=4.766,P<0.01), a decrease in the number of clone formation(t=16.02,P<0.000 1), a decrease in the proportion of proliferating cells(t=23.13,P<0.000 1), a decrease in cell migration rate(t=25.28,P<0.000 1), and a decrease in the number of small compartments(t=10.78,P=0.004). Conclusion BDH1is a characteristic gene for observing the sensitivity of PD-1 immunotherapy in HCC patients.BDH1could inhibit the proliferation, migration, and invasion ability of HCC cellsin vitro.