¹Centre for Research in Pharmaceutical Sciences, Sharda Bhavan Education Society's Nanded Pharmacy College, Nanded 431605, Maharashtra, India DOI : 10.29228/jrp.702 Inhibition of angiogenesis is one of the significant contrivance to suppress the developing tumor. Several previous studies have shown that phytochemicals can modify numerous vital processes of tumor promotion. However, there is no literature evidence of investigation on antitumor and antiangiogenic activity of Citrus karna Raf. fruit. It is used as folklore medicine for the treatment of various conditions like diabetic complications, gastro-intestinal disorders and neurological complication by the rural peoples in India. The present study was performed to investigate antitumor and antiangiogenic activity of Citrus Karna Raf. fruit peel. Among the different extracts, the CKME showed strong in vitro cytotoxic activity on Human Lung Cancer Cell line Hop2 and Human Hepatoma Cell line HepG2 in SRB assay. In Chick embryo chorioallantoic membrane (CAM) assay, angiogenesis processes is strongly inhibited by CKME and chrysin at 100 μg/disc. The formation of blood vessels is essential for fulfilling tumor growth requirements and transport of metastatically competent tumor cells that was reduced by CKME and chrysin. In silico PASS prediction showed that of Citrus Karna Raf. contains several phytochemicals that exhibit anticancer active by different mechanisms like inhibition of TNF expression and stimulation of apoptosis. In conclusion, the components of CKME are promising candidates for cancer treatment and further experimental investigations are needed in order to confirm their mechanism of action. Keywords : Antitumor drug screening assays; Antitumor agents; Angiogenesis inhibitors; CAM Assay; SRB Assay; Citrus Karna Raf