Abstract Three new flavonoids, which are isoprenylated by fused 2,2‐dimethyl‐3,4‐dihydro‐2H‐pyran moieties, were isolated from the roots of Sophora flavescens and named flavenochromanes A–C (1–3). Their structures were elucidated by spectroscopic methods, including 2D‐NMR techniques. Flavenochromane C (3) showed strong cytotoxic activity against A549 (lung carcinoma), 1A9 (ovarian carcinoma), KB (epidermoid carcinoma of the nasopharynx), and KB‐Vin (drug‐resistant variant KB) cell lines with IC50 values ≤1.7 μM, and significant activity against the MCF‐7 (breast adenocarcinoma) cell line with an IC50 value of 3.6 μM. Flavenochromane B (2) displayed slightly lower inhibitory effects (IC50 3.2–6.9 μM) as compared with 3.