To discover diterpenoids that naturally possess chemical weapons against cancer, the biological and chemical diversity of the flower buds of Daphne genkwa Sieb. et Zucc was investigated. Guided by LC-MS/MS analysis and the MetGem Molecular Networking, eight daphnane-type and tigliane-type diterpenoids including four new compounds were isolated. Spectroscopic elucidation and ECD quantum chemical calculations revealed their structures. All compounds were evaluated their cytotoxic activity of A549, Hep3B, and MCF-7 cell lines. Compounds 1 and 8 showed potent activity against the A549 and Hep3B cells.