Objective To study the chemical constituents of the sponge Haliclona cymaeformis collected from the South China Sea. Methods The compounds were isolated and purified by column chromatography on silica gel, reversed- phase silica gel (ODS) and Sephadex LH- 20, and their structures were elucidated on the basis of physicochemical and spectral analysis. Results Eleven compounds were isolated from the ethanol extract of H. Cymaeformis, and their structures were identified as 24- methylene-cholesta- 3β- ol (1), 5α,8β- epidioxy- cholesta- 6- en- 3- ol (2), cholesta- 7- en- 3β,5α,6β,9α tetraol (3), cholesterol (4), 1H- indole- 3- carboxylic acid (5), uracil (6), thymine (7), uridine (8), thymidine (9), 2- deoxyuridine(10), and 2- deoxythymidine (11), respectively. Conclusion All the isolated compounds were obtained from the sponge H. Cymaeformis for the first time. Compounds 3 showed significant inhibitory activities towards chronic myelogenous leukemia (K562) and human hepatoma (SMMC- 7721) cell lines.