Chronic HBV infection is a major cause of cirrhosis and hepatocellular carcinoma. Finding host factors involved in the viral life cycle and elucidating their mechanisms is essential for developing innovative strategies for treating HBV. The HBV core protein has pleiotropic roles in HBV replication; thus, finding the interactions between the core protein and host factors is important in clarifying the mechanism of viral infection and proliferation. Recent studies have revealed that core proteins are involved in cccDNA formation, transcriptional regulation, and RNA metabolism, in addition to their primary functions of capsid formation and pgRNA packaging. Here, we report the interaction of the core protein with MCMs, which have an essential role in host DNA replication. The knockdown of MCM2 led to increased viral replication during infection, suggesting that MCM2 serves as a restriction factor for HBV proliferation. This study opens the possibility of elucidating the relationship between core proteins and host factors and their function in viral proliferation.