Objective: The present study evaluates anticancer potential of caffeine using various pharmacological models. Methods: In case of In vitro hemolytic assay study the absorbance of the liberated hemoglobin and then checked % haemolysis using 450 nm λmax in UV spectrophotometer. In Brine shrimp lethality assay checked % mortality as well as counting the viable naupliis at different time intervals. In case of Allium cepa (Onion) root model checked physical or macroscopical parameters like root number, root length. To check the significance of data, ANOVA, Tuckey’s test, statistical tests were performed. P < 0.05 and highly significant at P <0.001. Statistical analysis was performed using INSTAT statistical software. Results: In vitro Hemolytic Assay shows concentration depended cytotoxic effect of Caffeine. When concentration of Caffeine increased % Hemolysis increased. In Brine shrimp lethality test shows concentration depended cytotoxic effect of Caffeine. Allium cepa (Onion) root model shows that caffeine reduce mitosis cell division process as it reduce number of root and number of length two different dose. Conclusion: Caffeine shows potential cytotoxic activities hemolytic, brine shrimp and Alium cepa models and can be use as safer, cheaper as well as lower toxic herbal alternative phytoconstitue in management of incurable disease like Cancer.