Methylation of histone H4 lysine 20 (H4K20) has been associated with cancer. However, the functions of the histone methyltransferases that trigger histone H4K20 methylation in cancers, including suppressor of variegation 4‑20 homolog 1 (Suv4‑20h1), remain elusive. In the present study, it was demonstrated that the knockdown of the histone H4K20 methyltransferase Suv4‑20h1 resulted in growth inhibition in chronic myeloid leukemia K562 cells. Disruption of Suv4‑20h1 expression induced G1 arrest in the cell cycle and increased expression levels of cyclin dependent kinase inhibitor 1A (p21WAF1/CIP1), an essential cell cycle protein involved in checkpoint regulation. Chromatin immunoprecipitation analysis demonstrated that Suv4‑20h1 directly binds to the promoter of the p21 gene and that methylation of histone H4K20 correlates with repression of p21 expression. Thus, these data suggest that Suv4‑20h1 is important for the regulation of the cell cycle in K562 cells and may be a potential therapeutic target for leukemia.