Abstract Objective To investigate the role of Hepatitis B surface antigen (HBsAg) in the immune escape of innate immunity by Hepatitis B virus (HBV). Methods After treated with PMA, THP-1 was differentiated into macrophage- like cells. Macrophage- like cells were treated further with LPS and the pam3csk4 in the presence or absence of HBsAg. Cytokine IL-10 , IL-12 protein, IL-10, IL-12 mRNA levels , NF-κB p65 protein nuclear translocation as well as IκB-α degradation and ERK protein phosphorylation were detected to monitor the activation of the TLR signaling pathway. Results LPS and the pam3csk4 induced production of cytokine IL-10 , IL-12 protein, NF-κB p65 protein nuclear translocation as well as IκB-α degradation and ERK protein phosphorylation were inhibited by HBsAg in a dose-dependent manner. Conclusion HBsAg inhibit the activation of TLR2 and TLR4 signaling pathway.