Three new sesquiterpenoid isopropylidene derivatives, named solajiangxins H and I (1 and 2) and 7-hydroxylsolajiangxin I (3), were isolated from the whole plant of Solanum lyratum. Their structures were elucidated on the basis of integrated spectroscopic techniques, mainly HR-FAB-MS, 1D NMR, and 2D NMR ((1)H-(1)H COSY, HMQC, HMBC, and NOESY). In vitro, compounds 1-3 were found to show significant cytotoxicity against three cancer cells (P-388, HONE-1, and HT-29), and gave IC50 values in the range of 3.2-7.7 μM.