Stem-loop binding protein (SLBP) is required for replication-dependent histone mRNA metabolism in mammals. Zebrafish possesses two , and is necessary for retinal neurogenesis. However, the detailed expression and function of in zebrafish are still unknown. In this study, we first identified zebrafish as an oocyte-specific maternal factor and then generated a maternal-zygotic F3 homozygous mutant (MZΔ4) using CRISPR/Cas9. The depletion of maternal Slbp2 disrupted early nuclear cleavage, which resulted in developmental arrest at the MBT stage. The developmental defects could be rescued in transgenic MZΔ4 embryos. However, homozygous mutant MZΔ1 developed normally, indicating is dispensable for zebrafish early embryogenesis. Through comparative proteome and transcriptome profiling between WT and MZΔ4 embryos, we identified many differentially expressed proteins and genes. In comparison with those in WT embryos, four replication-dependent histones, including H2a, H2b, H3, and H4, all reduced their expression, while histone variant significantly increased in MZΔ4 embryos at the 256-cell stage and high stage. Zebrafish Slbp2 can bind histone mRNA stem-loop in vitro, and the defects of MZΔ4 embryos can be partially rescued by overexpression of H2b. The current data indicate that maternal Slbp2 plays a pivotal role in the storage of replication-dependent histone mRNAs and proteins during zebrafish oogenesis.