Abstract: A series of NO-releasing alkoxylbiphenyl derivatives( 4a - 4g )were designed and synthesized by coupling the carboxyl group of alkoxylbiphenyl with NO donor. Their antitumor activities were evaluated by MTT assay in HepG-2, Bel-7402, SMMC-7721, QGY-7701 and Bel-7404 cell lines. The results indicated that the target compounds exhibited significant inhibitory effects on the proliferation of tumor cells, especially on HepG-2 cells(IC₅₀=1. 15-4. 34 μmol/L). Notably, the inhibitory effect of the target compounds on non-tumor liver LO2 cells was relatively weak(IC₅₀=5. 00-8. 53 μmol/L)except compound 4f , suggesting that these compounds have selective inhibitory effects on tumor cells in vitro. Additionally, compound 4b could significantly inhibit the parental sensitive K562 and drug-resistant K562/A02 cell proliferation, and the IC₅₀s were 1. 28 and 1. 32 μmol/L, respectively. Importantly, treatment with various concentrations of an NO scavanger significantly reduced the antitumor activity of compound 4b , suggesting that NO produced by compound 4b may play a significant role in inhi-biting the proliferation of K562 and K562/A02 cells.