Objective: To investigate the drug resistance reversing effect of gold nanoparticles (GNPs) on drug-resistant human hepatocellular carcinoma cell line. Methods: GNPs were synthesized by reducing hydrogen tetrachloroaurate using tri-sodium citrate, and identified. Adriamycin (ADM)-resistant hepatocellular carcinoma HepG2/ADM cells were treated with GNP and adriamycin (ADM), alone or in combination, using HepG2/ADM cells without any treatment as a control, and then the cell proliferation and apoptosis were determined by MTT assay and flow cytometry, respectively. The intracellular ADM concentration of HepG2/ADM cells after exposure to ADM alone or GNP plus ADM were determined by ultraviolet-visible spectrophotometer. Results: Compared with control cells, the cell proliferation was inhibited and apoptosis rate was increased significantly in HepG2/ADM cells treated with ADM along or combination with GNP, and these effects were more remarkable in the latter than in the former (all P<0.05). The intracellular ADM concentration in HepG2/ADM cells exposed to GNP plus ADM was significantly higher than in those exposed to ADM alone [(2.92±0.13) μg/L vs. (1.68±0.74) μg/L, P<0.05]. Conclusion: GNP can enhance the sensitivity of HepG2/ADM cells to ADM, and this effect may be related to its increasing the intracellular ADM accumulation in HepG2/ADM cells.