A rare type of sesquiterpene with a spiro bicyclic system (1) and seven new (2–8) and four known (9–12) β-santalol derivatives were isolated from the heartwood of Santalum album (Santalaceae). The structures of these new compounds were determined by analysis of extensive spectroscopic data. The isolated compounds and derivatives were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells, A549 human lung adenocarcinoma cells, HSC-2 and HSC-4 human oral squamous cell carcinoma cell lines, and TIG-3 normal human diploid fibroblasts. cis-β-Santalol (9) and β-santaldiol (10) induced apoptotic cell death in HL-60 cells.