ZCCHC4, which has been identified as the m6A RNA methyltransferase for 28S rRNA, is a novel regulator essential for RD histone mRNA translation. ZCCHC4 exhibits unexpected subcellular localization of cytoplasm besides nucleus and the cytoplasmic ZCCHC4 directly interacts with components of the translation initiation machinery. Depletion of ZCCHC4 reduces global protein translation, particularly the translation of RD histones. This translational impairment leads to insufficient histone supply, chromatin relaxation, and prolongs the S phase of the cell cycle.