Bio-activity directed investigation of hexane extract from the leaves of Premna tomentosa led to the isolation of three new clerodane diterpenes (1-3) along with four known compounds (4-7). The structures of new compounds were established using IR, MS, 1D, and 2D NMR techniques. The in vitro cytotoxicity of the crude hexane extract and the isolated compounds were evaluated against seven human cancer cell lines and results indicated that compounds 2 and 4 depicted significant cytotoxicity against hepatocellular carcinoma cell line.