The current investigation was carried out to examine the possible potential protective effects of ethanolic extract of annona fruit against trichloroacetic acid induced liver cancer. After completing the preparation of Anona fruit extracts, the HPLC conditions of phenols were estimated for each extract separately. The biological experiment used twenty- four albino rats. After the adaptation period, the rats were divided into six groups (6 rats each). One of them was considered as a negative control and another positive control (Trichloroacetic acid group). The remaining groups were divided into two groups consisting of mixture annona extracts at levels 100 and 150 mg / kg. Blood samples were collected to assays the levels of liver functions (ALT, AST, ALP, BIL, TP, ALB and GLB), kidney functions (creatinine and urea), and oxidation stress (CAT, GPX and MDA). Liver tissues were collected for inflammation markers analyses (IL6, AFP, COX2 and PGE2) and histopathology analysis. The study results were as the fallowing: all liver cancer protected groups marked a significant improvement in liver functions, kidney functions, oxidation stress, inflammation markers and histopathological results when compared them with the unprotected liver cancer group (+ve). Therefore, this study recommends that the insertion annona fruit in diets because its hepatoprotective, anti-cancer and antioxidants effects. Therefore, we recommend including it in the diet because it contains phenols that act as powerful antioxidant that protect the body's cells from inflammations.