Ethnopharmacological relevance: Chong-lou (Paris polyphylla var. yunnanensis or P. polyphylla var. chinensis) is traditionally used as an anticancer medicine in China. It is also the material basis of some Chinese patent anticancer medicines, such as Gan-Fu-Le capsules, Bo-Er-Ning capsules, Lou-Lian capsules, Ruan-Jian oral liquid, and Qi-Zhen capsules. P. forrestii, a substitute for Chong-lou, is planted at a large scale in the Yunnan Province of China.& para;& para;Aim of the study: To clarify the active chemical constituents of P. forrestii and evaluate the in vitro and in vivo anticancer activities of the total saponins from P. forrestii.& para;& para;Materials and methods: The total saponins of P. forrestii were extracted and separated to yield pure compounds by chromatographic techniques, and the structures of the isolates were elucidated by spectroscopic methods. The cytotoxicity of the crude extracts, total saponins, and chemical constituents were evaluated using an MTS assay. In vivo antitumor activities of the total saponins from P. forrestii were measured using H22 tumor-bearing mice by intraperitoneal (ip) administration.& para;& para;Results: Eight compounds, including polyphyllin D (1), formosanin C (2), dioscin (3), diosgenin-3-O-alpha-L--rhamnopyranosyl-(1 -> 2)-[beta-D-glucopyranoside (4), paris saponin H (5), pennogenin-3-O-alpha-L-rhamnopyranosyl-(1 -> 2)-[alpha-L-rhamnopyranosyl-(1 -> 4)]-beta-D-glucopyranoside (6), pariposide A (7), and crustecdysone (8), were isolated from the total saponins of P. forrestii. The total saponins and compounds 1-6 showed significant inhibitory activity against the growth of the HL-60, SMMC-7721, A 549, MCF-7, and SW480 cell lines. The total saponins from P. forrestii had a tumor-inhibitory effect in H22 tumor-bearing mice upon ip (2.25 mg/kg dose) administration, with an inhibition rate of 42.6% compared with cisplatin (ip, 2 mg/kg dose, 53.9% inhibition rate). & para;& para;Conclusion: The results support that P. forrestii could be a substitute for P. polyphylla var. yunnanensis as an anticancer medicine.