The main aim and objective of the present research work was the preliminary phytochemical screening and evaluation of in vivo anti tumour activity of mthanolic and ethyl acetoacetate extracts of fruit of Punica granatum (ME-FPG and EAAE-FPG). Acute oral toxicity of ME-FPG and EAAE-FPG were performed according to the OECD guideline 423 method. The experimental results of acute oral toxicity studies revealed that all the extracts proved to be non toxic at tested dose levels and well tolerated by the experimental animals as there LD50 cut of values > 2000 mg/kg b. w. The in vivo antitumor activity of ME-FPG and EAAE-FPG was carried out against human colon cancer cell line HT 29. The present in vivo experimental data displayed that both ME-FPG and EAAE-FPG significantly increased the PILS. While 5-FU increased the life span of 85%, ME-FPG increased it by 75% and 67.5% by EAAE-FPG respectively ME-FPG. So ME-FPG and EAAE-FPG at dose 300 mg/kg significantly improved the overall survival of treated animals in comparison to tumour control group and 5-FU was not significantly differed from each other in improving the overall survival of animals. Histopathological study displayed a greater degree of tumour apoptosis and necrosis in the ME-FPG and EAAE-FPG treated group than in the control group. In addition, PCNA showed that administration of ME-FPG and EAAE-FPG decreased the proliferation of tumour tissues. Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication