This study aimed to improve encapsulated doxorubicin ENC-DOX efficiency via loading into pectin nanoparticle PNPs and to investigate the antitumor efficacy of Doxorubicin DOX and ENC-DOX in Ehrlich Ascites Carcinoma EAC bearing-mice. ENC-DOX was optimally fabricated and characterized; female albino mice were divided into 6 groups group 1: control CON, group 2: EAC induced by once injection of 2.5 x 106 EAC/ml, group 3: EAC+DOX received 12mg/kg of DOX i.p, group 4: EAC+PNPs received orally 12mg/kg PNPs, group 5: EAC+DOX+PNPs as the same previous dose and route, and group 6: EAC+ENC-DOX received 12mg/kg of ENC-DOX orally. The treatment with ENC-DOX resulted in a significant reduction in mean tumor weight MTW, improvement in mean survival time MST, and an increase in life span ILS. Also, ENC-DOX ameliorated the cardiac CK and LDH and decreased MDA levels associated with improvement in GPX, GSH, and SOD levels and reduced the level of TNF-α and MCP-1; also, ENC-DOX caused depletion in caspase-3 and P53 with an elevation of Bcl2 level comparing with treatment with free DOX, dimensioned histological lesions were noticed in the heart tissue sections of mice administrated ENC-DOX. The treatment of EAC mice with ENC-DOX displayed a promising potential antitumor effect with greater safety than free DOX.