The incidence of cancer is on the increase worldwide, and there are concerns of selectivity of action and significant deleterious effects associated with existing anticancer drugs. Based on these facts, tremendous effort is being made worldwide to discover and develop new anticancer agents with better efficacy and safety profile. In this study, various extracts of Byrsocarpus coccineus, a Nigerian medicinal plant, were evaluated for antiproliferative activity in in-vitro and in-vivo assays. The sulforhodamine B (SRB) (in-vitro) using A549 (lung), HCT-116 (colon), PC3 (prostate), A431 (skin), HeLa (cervix), THP-1 (leukemia), NCI-H322 (lung), and COLO-205 (colon) human cancer cell lines, Sarcoma-180 (S-180) ascites and L1210 lymphoid leukemia (in-vivo) antiproliferative assays were used in this study. Based on the standard of 30 µg/mL as the upper IC50 limit for purification of crude extracts, BC-A001 (ethanolic extract; IC50 12 µg/ml with A431); BC-A002 (hydroethanolic extract; IC50 125% considered to depict activity). The results obtained in this study suggest that the extracts of B. coccineus possess significant antitumor activity in-vitro against skin, lung, colon and prostate human cancer cell lines with BC-A002 demonstrating moderate activity in the S-180 ascites model with no activity in the L1210 lymphoid leukemia test.