Natural products particularly microbial metabolites have been the mainstay of cancer chemotherapy and are likely to provide many of the lead structures and derivatives with new biological activities. In this research, the production of some potential cytotoxic metabolites from Streptomyces (S.) griseus isolate KJ623766 was carried out in 1 4 L laboratory fermenter under specified optimum conditions (28°C temperature, 200 RPM rotation speed, uncontrolled PH, 3 vvm aeration and 2 bar airflow pressure). Using 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay, the cytotoxic activity of the ethyl acetate (1:1, v/v) extract of cell free culture supernatant (CFCS) against Caco2 and Hela cancer cell lines was determined with CD 50 of 14 µg/ml and 20 µg/ml, respectively. Bioassay guided fractionation of the ethyl acetate extract using different chromatographic techniques had led to the purification of the cytotoxic metabolites coded W1, R1 and R2 with reproducible amounts of 20, 5, and 1.5 mg/l, respectively. The structures of respective metabolites were determined using various spectroscopic analysis and identified as genistein, β-rhodomycinone and γ- rhodomycinone, respectively. Accordingly, S. griseus isolate KJ623766 can be used as a potential industrial strain for the large scale production of the isoflavonoid genistein, as well as for the production of β-and γ- rhodomycinone to be used for the construction of new derivatives with more potent cytotoxic activities of the anthracycline family. This is the first report about the production of the isoflavonoid genistein by S. griseus KJ623766.