The medicinal plant Annona muricata of the Annonaceae family, also called Graviola, native to the Andean highlands of Peru and Ecuador but also widespread in Chile, California, Florida, southern Africa and various Mediterranean countries, has various beneficial properties for health and has been the subject of several studies for its anti-tumor activity. In this work, a phytochemical analysis of the aqueous extract of Annona muricata by using HPLC technique to evaluate the content of total polyphenols, flavonoids and tannins, was performed. In addition, for the first time, an evaluation of the effect of the aqueous extract on a Dba/2 transgenic mouse model carrying a P815 tumor, was established. Following the administration of oral doses of 250 and 500 mg/kg for 30 days, a decrease in the volume and weight of the tumors was detected. Furthermore, a correlation between the reduction of oxidative stress and the anticancer properties of Annona muricata, was demonstrated. In conclusion, the aqueous extract of Annona muricata may provide a new therapeutic approach to manage unwanted growth of mastocytoma (P815 tumor) by targeting oxidative stress.