Objective To explore whether aspirin could sensitize arsenic trioxide on human hepatocelluar carcinoma cell line and understanding the combination mechanisms underlying co-treatment. Methods Cell viability was detected by MTT assay, cell apoptosis rate and reactive oxygen species (ROS) level were measured by flow cytometry, and Western blot assay was used to estimated the protein expression of heme oxygenase-1 (HO-1) in total protein and NF-E2-related factor 2 (Nrf2) in nuclear protein. Results 10 μmol/L arsenic trioxide can decreased the cell viability, while cell apoptosis rate, ROS level, HO-1 and Nrf2 protein expression was increased ( P