Early studies have shown that autophagy and TPPII are associated with HBV infection. In this study, adenovirus vector containing TPPII was constructed to immunize HBV transgenic mice in vivo to explore the potential mechanism of autophagy and HBV infection. Our goal is to provide new ideas for immunotherapy of hepatitis B. First, adenovirus vector containing TPPII was constructed. Then we used adenovirus to immunize HBV transgenic mice and ATG5 knock-out HBV transgenic mice. The autophagy of CD8 +T cells was detected by transmission electron microscopy and immunofluorescence electron microscopy, western blot was used to detect the expression of autophagy LC3 and BECN-1, CTL reaction, HBV DNA and HBsAg in serum, HBsAg and HBcAg in liver tissues byimmunohistochemistry, to further examine the possible mechanisms involved in autophagy. Adv-HBcAg-TPPII promotes autophagy of CD8 + T lymphocyte, activates CTL response, inhibits HBV DNA replication and HBsAg expression, and PI3K/ Akt /m TOR signaling pathway may be involved in autophagy. This study demonstrates that autophagy of CD8+T cells was induced by Adv-HBcAg-TPPII and the molecular mechanism may be related to the PI3K/ Akt /m TOR signaling pathway, providing a possible theoretical basis for immunotherapy of hepatitis B.