This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma (HCC), further, to explore the effect of LPCAT1 on overall survival (OS) in patients with HCC, and its possible mechanism. Bioinformatics analysis using high throughput RNA-sequencing data from TCGA was utilized to explore the differential expression of LPCAT1 between normal and tumor tissues, and the associations between LPCAT1 expression and clinicopathological parameters. Survival analyses and subgroup survival analyses were utilized to elucidate the effect of LPCAT1 on OS in patients with HCC. Univariate analysis and multivariate analysis were used to investigate the prognostic factors. Potential LPCAT1 related tumor genes were identified by the methodology of differentially expressed genes (DEGs) screening. GO term enrichment analysis, KEGG pathway analysis and the PPI network were used to explore the potential mechanism. LPCAT1 was significantly overexpressed in HCC tumor tissues compared with normal tissues. The LPCAT1 expression was related to tumor grade, ECOG score, AFP and TNM stage, with p values of 0.000, 0.000, 0.007 and 0.000, respectively. Multivariate analysis demonstrated that LPCAT1 expression was independently associated with OS, with an HR of 1.04 (CI: 1.01–1.06, p = 0.003). The KEGG pathway enrichment analyses showed that overlapped DEGs mainly participate in the cell cycle. Finally, we identified a hub gene, CDK1, which has been reported to act on the cell cycle, consistent with the result of KEGG enrichment analysis. Collectively, these data confirmed LPCAT1 was upregulated in HCC, and was an independent predictor of the prognosis. © 2020 Chongqing Medical University