Aim: To research the influence and mechanism of gold nanoparticles (AuNPs) with different size for HK-2 cells (kidney normal cells) and 786-0 cells (kidney cancer cells). Materials & methods: HK-2 cells and 786-0 cells were treated with 5 and 200 nm AuNPs at 1 and 10 μg/ml. The cell viability, intracellular reactive oxygen species levels, cell apoptosis, cell autophagy, and related cell signaling pathways were analyzed. Results: In HK-2 cells, AuNPs reduced the activity of Akt and mTOR and upregulated the expression of LC3 II. In 786-0 cells, the activity of p38 was upregulated, which leaded to the increase of caspase 3 and initiated apoptosis. Conclusion: AuNPs of 5 and 200 nm at 10 μg/ml exerted antitumor effect by prompting apoptosis and inhibiting proliferation, while autophagy was activated to protect HK-2 cells from AuNPs-induced cytotoxicity.