Objective To investigate the role of LncRNA HULC in hepatoma cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) via the miR-372 / CXCR4 axis. Methods The online bioinformatics TargetScan database was used to predict target genes. Cell transfection was used to establish gene overexpression and silencing cell models. qRT-PCR and Western blot were used to detect gene and protein expression, respectively. CCK-8 assays were used to assess cell viability. Cell colony formation assays were used to analyze cell proliferation. Annexin V-FITC/ PI was used to analyze apoptosis. Immunohistochemical staining was used to detect expression of proteins. Results In liver cancer tissues and cells, HULC and CXCR4 expression was upregulated, and miR-372 expression was downregulated. TargetScan database analysis and dual luciferase assays revealed a relationship between miR-372 and HULC or CXCR4. CCK-8 assays showed that HULC and CXCR4 increased cell viability, and miR-372 inhibited cell viability. Colony formation assays showed that HULC and CXCR4 promoted cell proliferation, and miR-372 inhibited cell proliferation. Flow cytometry showed that HULC and CXCR4 inhibited apoptosis, and miR-372 promoted apoptosis. Western blot analysis showed that HULC and CXCR4 inhibited the expression of E-cadherin and promoted the expression of Vimentin, while miR-372 promoted the expression of E-cadherin and inhibited the expression of Vimentin. Conclusions HULC inhibits the expression of miR- 372, thereby promoting CXCR4 expression, proliferation, and EMT progression of hepatoma cells, while inhibiting apoptosis .