Zinc sulfate (ZnSo4) is an inorganic compound. Zinc is used to treat and prevent zinc deficiency. Zinc is a naturally occurring mineral that is important for growth and the development and health of body tissues. In this study, specific concentrations of ZnSo4 on cell viability were investigated by MTT method in hepatocellular carcinoma (HepG2), lung cancer (A549), and normal lung cell (Wi38). Cell cycle arrest and apoptosis were measured by flow cytometry assessment by PI Staining and Annexin V/PI Staining, respectively. Results showed that Zinc induced cytotoxicity in HepG2, A549, and Wi38 using different concentrations (IC50 = 308.11, 413.02, 463.15 μg/ml). These data indicated that ZnSo4 decreased cell viability in malignant and non-malignant cells and confirmed the occurrence of their cytotoxic effects. Cell cycle and apoptosis by flow cytometry showed a significant increase in ZnSo4 -damaged HepG2 cells by cell cycle arrest in the G2/M phase and increased apoptosis. In addition, the mRNA expression levels of p53 and casp3 increased while Bcl-2 decreased in HepG2 cell lines when treated with a high concentration of ZnSo4. The effects of ZnSo4 on different yeast haploid knockout strains were evaluated in this study (YKO). We used the Comet assay method of the three different concentrations of ZnSo4 at which this set of ZnSo4 could cause DNA damage. The comet assay exhibited a better sensitivity of yeast cells, which was undeniably confirmed. The genotypes of YKO were chosen based on the (Clustal Omega Multiple Sequence Alignment EMBL-EBI) alignments of human and yeast gene sequence homology.