Abstract: Objective: To explore the molecular mechanism and immune environmental characteristics of hepatocellular carcinoma (HCC) with hepatic trematodiasis using transcriptomic data. Methods: The cancerous tissue and adjacent tissue samples from 6 HCC patients (3 patients with hepatic trematodiasis and 3 patients without hepatic trematodiasis) who underwent surgical resection in the First Affiliated Hospital of Guangxi Medical University from January 2022 to December 2023 were collected for transcriptome sequencing. The gene expression profiles of HCC patients with and without hepatic trematodiasis were compared, "Limma" package was used to identify differentially expressed genes (DEGs), and functional enrichment (GO) analysis of these genes was performed to determine the biological pathways involved. Cibersort algorithm was used to precisely quantify immune cell infiltration patterns in the tumor microenvironment of HCC patients and construct protein-protein interaction (PPI) networks to reveal the potential interactions and signaling mechanisms between these DEGs. Results: A total of 131 DEGs and 31 Hub gens were identified in HCC patients with hepatic trematodiasis, all of which were related to metabolic and inflammatory signaling pathways. Immunological analysis revealed an upregulation of T cells CD4⁺ memory resting infiltration in the tumor tissues of HCC patients with hepatic trematodiasis. Conclusion: Reprogramming of metabolic pathways, aberrant activation of inflammatory signaling pathways, and alterations in the immune microenvironment may collectively constitute contribute the potential biological basis for the poor prognosis of HCC patients with hepatic trematodiasis.