〔Abstract〕 To investigate the expression level of LONP1 in hepatocellular carcinoma ( HCC) and its impact on the occurrence and progression of HCC . Methods The expression of LONP1 in human liver cancer tis- sues was verified by real-time quantitative PCR (qPCR) and Western blot. LONP1 stable knockdown Hep3B and HCCLM3 cell lines were established , and the effects of LONP1 on cell proliferation were explored through Cell Counting Kit-8 (CCK-8) , EdU incorporation assays , and colony formation assays . The effects of LONP1 on cell migration were assessed using scratch and Transwell migration assays . A Cre-Loxp system was employed to generate LONP1 conditional knockout mice , and transcriptomic sequencing of liver tissues was performed to explore the im- pact of LONP1 deficiency on liver cells . The effects of LONP1 on apoptosis in hepatocellular carcinoma cell lines were explored using Tunel staining and flow cytometry with Annexin V-FITC/PI . Results Western blot and qPCR experiments confirmed the high expression of LONP1 in human liver cancer tissues . Colony formation assays re- vealed that the number of cell clones in LONP1 knockdown groups was significantly reduced compared to the control (P < 0. 01) . CCK-8 and EdU assays demonstrated that LONP1 knockdown cells had a significantly lower prolifera- tion rate than control cells (P < 0. 01) . Scratch and migration assays showed that LONP1 knockdown liver cancer cells exhibited impaired migration compared to controls (P < 0. 01) . Transcriptomic analysis of liver tissues from LONP1 conditional knockout mice indicated that LONP1 might affect apoptosis pathways in liver cells . Tunel stai- ning and Annexin V-FITC/PI flow cytometry showed that LONP1 knockdown increased apoptosis in hepatocellular carcinoma cells . Conclusion LONP1 is highly expressed in liver cancer tissues . The knockdown of LONP1 in liv- er cancer cell lines promotes cell apoptosis and inhibits cell proliferation and migration .