Abstract: Curcumin has a concentration based effect on normal cells and its mechanism of action is very intriguing. Effect of various concentrations of curcumin on wild type Schizosaccharomyces pombe cells was studied with an aim to evaluate possibility of combining curcumin with chemotherapeutic drugs and to gain an insight into its mechanism of action in normal cells. Effect of 5-fluorouracil or curcumin independently and in combination on cell growth, reactive oxygen species generation, antioxidant enzyme activity, DNA integrity and cell cycle arrest were studied. Curcumin at 5 μM and above concentrations reduced the cell growth, increased reactive oxygen species and arrested the cell cycle in G1/S phase in untransformed cells. Treatment of 5-fluorouracil also reduced cell growth and led to increased reactive oxygen species. However, combination of lower concentration of curcumin with 5-fluorouracil could control reactive oxygen species levels and prevent DNA damage. The cells never entered into apoptosis due to curcumin treatment up to 10 μM concentration, as observed by DNA pattern in gel. Curcumin prevented the DNA damage by activation of natural antioxidation mechanism in cells as observed by increase in total glutathione level and catalase activity. In conclusion, curcumin showed concentration based effect on growth of S. pombe cells and its combination with 5-flurouracil was found to be beneficial in controlling the cell growth and toxic reactive oxygen species levels.