Drug resistance and poor prognosis in hepatocellular carcinoma (HCC) underscore the urgent need for novel treatments. Disulfidptosis, a recently identified form of metabolism-related regulated cell death, plays a complex role in anti-tumor immunity; however, its precise function in HCC remains unclear. Understanding the proteins and pathways involved in disulfidptosis and its association with disulfidptosis-related genes (DRGs) in HCC could reveal innovative therapeutic strategies. This study employs bioinformatics to examine the correlation between DRGs and both clinical prognosis and immune status in HCC patients. Risk models were constructed using univariate Cox and least absolute shrinkage and selection operator regression to identify significant genes, with risk scores correlated to survival outcomes across various patient subtypes. In addition, the analysis explored the association of DRGs with prognosis, immune cell infiltration, enriched functional pathways, and immune checkpoints. The risk model identified six key genes: FLNA, NCKAP1, CD2AP, RPN1, SLC7A11, and CAPKAP. Validation through the receiver operating characteristic curve demonstrated the model’s exceptional predictive power. Gene network analysis revealed ten essential genes, three of which (FLNA, CD2AP, and CAPZB) were shared with the risk model. FLNA and CAPZB have previously been linked to therapeutic indicators and pathways in HCC. However, there is a lack of comprehensive data connecting CD2AP to clinical therapy or HCC pathways. These findings highlight the significance of DRGs in HCC prognosis and immune regulation, suggesting that DRG-targeted therapies may offer new avenues for HCC treatment.

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