<b>Methods</b>: We investigated the roles of lncRNA PCNAP1 in contribution of HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling in hepatocarcinogenesis by using CRISPR/Cas9, Southern blot analysis, confocal assays, <i>et al.</i> in primary human hepatocytes (PHH), HepaRG cells, HepG2-NTCP cells, hepatoma carcinoma cells, human liver-chimeric mice model, transgenetic mice model, <i>in vitro</i> tumorigenicity and clinical patients.