Abstract: This study is aimed at assessing the role of the interaction between a Nigerian-Like Diet (NLD) or Western-Like Diet (WLD) and aspirin on energy metabolism and ATPases in early colon carcinogenesis. We observed that the WLD significantly (p< 0.05) increased intestinal length of rats compared with the NLD and interaction with aspirin slightly reversed this effect. The study also reports that the WLD increased the activities of some enzymes of energy metabolism compared with the NLD and that this increase is more than tripled with the inclusion of cycas in the diet. Aspirin administration reduced the activities of these enzymes more in the rats fed with the WLD than the NLD. We also observed that like the WLD, cycas inclusion in the diet of rats significantly raised the activity of Mg2+ ATPase (9% in the NLD and 34% in the WLD) and decreased Ca2+ ATPase (30% in the NLD to 42% in the WLD). Aspirin reversed these effects of cycas on these ATPases (37% in the NLD and 40% in the NLD for Ca2+ ATPase). This study demonstrates that an increase in Mg2+ ATPase and a decrease in Ca2+ ATPase is associated with early colon carcinogenesis and that while the WLD promotes these enzyme changes, the NLD have the opposite effect. The study also reveal that aspirin effect on the enzymes of energy metabolism and ATPases supports its protective role against colon carcinogenesis and that the effect of the drug is dependent on the protein content of the diet.