Present studies indicated that NCAPD2 (Non-SMC condensin I complex subunit D2) has emerged as an essential participant of condensin I involved in the mitotic chromosome assembly and dissociation. However, its comprehensive role in pan-cancer and its underlying mechanisms remain underexplored. This study systematically analyzed NCAPD2's prognostic significance, functional mechanisms, and immune infiltration correlations in pan-cancer, with a focus on hepatocellular carcinoma (HCC). Using databases such as TCGA, TIMER2.0, and HPA, we evaluated NCAPD2's association with oncogenesis, prognosis, methylation, and immune infiltration. Experimental techniques, including BrdU, Transwell, flow cytometry, RT-qPCR, western blotting, and immunofluorescence, were employed to investigate NCAPD2's functional role. Results revealed that NCAPD2 is aberrantly expressed in multiple cancers, with upregulation linked to poor prognosis. NCAPD2 mutations, methylation changes, and microsatellite instability were also observed in various cancers. In HCC, NCAPD2 expression correlated significantly with immune cell infiltration and immunotherapy response. Mechanistically, NCAPD2 knockdown suppressed HCC cell proliferation, induced G0/G1 phase arrest, and promoted apoptosis. Additionally, NCAPD2 facilitated liver cancer cell migration and regulated the cell cycle via the AKT/GSK-3β signaling axis. Silencing NCAPD2 inhibited AKT and GSK-3β phosphorylation while upregulating p21 expression. In conclusion, NCAPD2 is a potential diagnostic and prognostic marker in pan-cancer, particularly for HCC. It promotes tumor progression through the AKT/GSK-3β pathway and influences immune infiltration, offering insights for immunotherapy and precision medicine strategies in HCC.