Background: Ehrlich Ascites carcinoma (EAC) is one of the commonest tumors that found in mice as a form spontaneous murine mammary adenocarcinoma adapted to ascites form. Aims: In this study we aimed to investigate the possible effect of guava leaves extract on HepG2 cells, MCF-7 cells, HCT cells, and A549 cells in vitro, also determination of cell cycling arrest on HepG2 cell line, and HPLC analysis of Guava leaves extract for phenolic and flavonoid compounds, and measuring the antioxidant activity of Guava leaves extract, and effect of Guava leaves extract on EAC in Swiss albino mice in vivo. Material and method: The antitumor effect was assessed by evaluating tumor volume, tumor cell count. We assessed the effect of Guava leaves extract on (ALT), (AST), Albumin, TP, urea, Creatinine, (CK activity), (CK-MB activity); Apoptosis was assessed by Osteopontin and caspase3 activity. Results: Our results indicated that Guava leaves extract have on HepG2 cell line and MCF7 cell line; also result indicated that Guava leaves extract have anti-inflammatory effect on mice by decrease liver enzyme and decrease Kidney functions and heart enzyme; Guava leaves extract also have anti-tumor effect on EAC in treated mice by inhibiting non apoptotic protein Osteopontin and increase apoptotic protein Caspase-3. Conclusions: Therefore this study strongly indicates that the Guava leaves extract can be considered as attractive candidates in therapeutic strategy of liver cancer and breast cancer development