Collectively, these data demonstrate that CCNL1 promotes HBV transcription and replication through modulation of RNAPII phosphorylation and chromatin-associated transcriptional activity, identifying CCNL1 as a potential host susceptibility factor for HBV.<h4>Importance</h4>Hepatitis B virus infection remains a major threat to human health in areas with high prevalence. Here, CCNL1 is linked to hepatitis B virus infection.