Objectives: We investigated the molecular underpinnings of miR-205-3p in driving the proliferative behavior of endothelial cells originating from hepatocellular carcinoma (HCC). Methods: In our study, reverse transcription quantitative PCR analysis identified a significant upregulation of miR-205-3p in endothelial cells from HCC. This upregulation was consistently observed across various HCC cell lines and tissue samples. Further investigation highlighted the regulatory effect of miR-205-3p on the HINT1 gene. The interaction between miR-205-3p and the 3’ untranslated region of HINT1 was confirmed using a dual-luciferase reporter assay. Additionally, experiments involving MTT assays and flow cytometry demonstrated that lentivirus-mediated suppression of HINT1 enhanced cellular proliferation and reduced apoptotic activity in HCC cell models. Results: This study reveals that miR-205-3p contributes to the progression of endothelial cells from HCC by targeting and inhibiting HINT1, a tumor suppressor. Conclusions: This study provides a theoretical foundation suggesting that miR-205-3p may serve as a viable molecular target for gene therapy interventions in clinical settings.