Therefore, we proposed a two-step hypothesis in which HBV results in the occurrence of DLBCL: first, the sustained chronic infection (HBV infection) leads to the overexpression of PD1 on T lymphocytes, leading to the exhaustion of activated T cells and inhibition of the immune system in the infected area; and second, persistent HBV infection generates mutations in infected B lymphocytes, and when the immune system is compromised, mutated B lymphocytes evolve into DLBCL over a period of time. This evidence concerns the gene PDCD1 and diffuse large B-cell lymphoma.