〔Abstract〕 Objective To verify the mRNA that inhibits the replication and expression of hepatitis B virus(HBV) in hepatocytes. Methods The peroxisome proliferator activated receptor(PPAR) α(PPARα), nuclear factor B(NFIB) and interleukin-8(IL-8) genes were transferred into HepG2.2.15 and HBV whole genome 1.3 ploid HepG2(HBV1.3 P-HepG2) cell models by lentiviral mediation. 48 hours after transfection, mRNA expression and HBVDNA replication level were detected by qPCR with blank control group(NC) as control. The expression of HBsAg and HBeAg in the cell supernatant was detected by chemiluminescence, and the expression of HBsAg in the cells was detected by immunofluorescence. Results In HepG2.2.15 and HBV1.3 P-HepG2 cell models, PPARα could promote the replication of HBVDNA and the expression of HBsAg, and the expression of HBVDNA was 1.46 and 1.27 times higher than that of NC group(P<0.05). NFIB could inhibit the replication of HBVDNA and the expression of HBsAg, and the expression of HBVDNA was 0.76 and 0.55 times higher than that of NC group(P<0.05). IL-8 could promote the replication of HBVDNA and the expression of HBsAg, and the expression of HBVDNA was 1.54 times and 1.62 times higher than that of NC group(P<0.05). Conclusion PPARα and IL-8 in hepatocytes can promote the replication and expression of HBV, while NFIB can inhibit the replication and expression of HBV, which can provide laboratory basis for follow-up research.