The plants have been used as drugs for centuries. However, limited research has been done on its great potential as sources of new therapeutic agents. The purpose of this study was to evaluate Physalis peruviana cytotoxic activity on cell lines HT-29, PC-3, K-562 and VERO. The HT-29 cell lines, PC-3, K-562 and VERO, were exposed to four concentrations of P. peruviana ethanolic leave and stem extracts, also at different concentrations of cisplatin and 5-fluorouracil (5-FU), which were used as positive controls. We found rates of growth within 48 hours, then we determined the inhibitory concentration 50 (IC50) using linear regression analysis and the index of selectivity of each sample. The P. peruviana ethanolic leave and stem extracts showed cytotoxic activity. The IC50 in g/mL in leaves and stems were, 0.35 (r =-0.95 p <0.025) and 0.37 (r =- 0.90 p <0.05 ) for HT-29; 0.87 (r =-0.98 p <0.01) and 1.01 (r =-0.95 p <0.025) for PC-3; 0.02 (r =-0.98 p <0.01) and 0.03 (r =-0.98 p <0.01) for K-562; 4.9 (r =-0.95 p <0.025) and 6.2 (r =-0.98 p <0.01) for VERO. The IC50 for antineoplastic were: for cisplatin: 4.2 (r =-0.96 p <0.025), 10.3 (r =-0.97 p <0.025), 0.15 (r =-0.98 p = 0.01) and 1.1 (r =- 0.98 p = 0.01); for 5-FU: 2.3 (r =-0.97 p <0.025), 17.9 (r =-0.95 p <0.025), 0.15 (r =-0.98 p = 0.01) and 1.1 (r =-0.94 p = 0.05) for HT-29, PC-3, K562 and VERO respectively. The leaves and stems extracts selectivity index were between 5.6 and 245 for tumor cell lines evaluated, by contrast, cisplatin and 5-FU, only showed values between 0.11 and 7.3. The P. peruviana leaves and steams ethanolic extracts were more cytotoxic than cisplatin and 5 FU, on the lines HT-29, PC-3 and K562. Furthermore the P. peruviana cytotoxic effects were less than cisplatin and 5-FU for VERO control cells lines.