ThePaeonia suffruticosa, known as ‘Feng Dan’, has been used for thousands of years in traditional Chinese medicine. In our chemical investigation on the root bark of the plant, five new phenolic dimers, namely, paeobenzofuranones A–E (1–5), were characterized. Their structures were determined using spectroscopic analysis including 1D and 2D NMR, HRESIMS, UV, and IR, as well as ECD calculations. Compounds2,4, and5showed cytotoxicity against three human cancer cell lines, with IC50values ranging from 6.7 to 25.1 μM. Compounds1and2showed certain inhibitory activity on NO production. To the best of our knowledge, the benzofuranone dimers and their cytotoxicity ofP. suffruticosaare reported for the first time in this paper.