Objective To investigate the expression and clinical significance of tripartite motif-containing 7 (TRIM7) in hepatocellular carcinoma (HCC), and to explore the molecular mechanism by which TRIM7 regulates mitochondrial function via nuclear factor erythroid 2-related factor 2 (Nrf2) to promote HCC progression. Method The expression and prognostic value of TRIM7 in HCC were analyzed using the TCGA database. Stable Huh7 cell lines were constructed, including the shTRIM7 group, Nrf2 overexpression group, and shTRIM7+Nrf2 rescue group. Mitochondrial function indicators were detected, including mitochondrial complex I activity, ATP content, reactive oxygen species (ROS) level, mitochondrial membrane potential, GSH/GSSG ratio, and NAD+/NADH ratio. Cell proliferation, migration and apoptosis were measured by CCK-8, EdU, Transwell and flow cytometry. The interaction and ubiquitination of TRIM7 and Nrf2 were verified by co-immunoprecipitation (Co-IP) and ubiquitination assays. Protein expression was determined by Western blot. Results TRIM7 expression was significantly higher in HCC tissues than in normal liver tissues (P<0.001), and high TRIM7 expression was associated with shorter overall survival in HCC patients (P<0.05). Genes co-expressed with TRIM7 were significantly enriched in mitochondrial function and oxidative stress pathways. Compared with the Con group,the shTRIM7 group showed significantly decreased complex I activity and ATP content, along with increased ROS levels, elevated mitochondrial membrane potential depolarization ratio, and decreased GSH/GSSG and NAD+/NADH ratios (all P<0.05), along with markedly suppressed proliferation, migration and enhanced apoptosis (all P<0.05). Mechanistic studies confirmed that TRIM7 directly interacted with Nrf2 and mediated Nrf2 ubiquitination to maintain its protein stability. Nrf2 overexpression significantly reversed shTRIM7-induced mitochondrial dysfunction and suppression of malignant phenotypes (all P<0.05). TCGA analysis revealed a significantly positive correlation between TRIM7 and Nrf2 expression (R=0.2, P<0.001), and both were associated with poor prognosis in HCC patients. Conclusion TRIM7 stabilizes Nrf2 expression by mediating its ubiquitination, maintains mitochondrial homeostasis, and thereby promotes proliferation and migration while inhibiting apoptosis in HCC.