mRNAs required for meiotic maturation and early embryonic development are stored in growing oocytes. These transcripts are translationally repressed until hormonal cues trigger ovulation. Errors in translation underlie some cases of human infertility and are associated with ovarian germ cell tumors. However, it remains unclear how maternal transcripts are kept quiescent in mammals. This study describes a potential translational regulator, KHDC1B. KHDC1B is a member of a small family of KH-domain containing proteins specific to eutherian mammals. Two family members, KHDC1A and 1B, are highly expressed in oocytes. KHDC1A and 1B bind polyU agarose and form oligomers like other KH-domain proteins. The functions of these proteins were tested by expression in Xenopus embryos. KHDC1A caused cell death, whereas KHDC1B caused cleavage arrest. This arrest phenotype was rescued by coexpression of the mouse translational regulator cytoplasmic polyadenylation binding protein 1 (mCPEB1). Coimmunoprecipitation and coimmunostaining experiments confirmed the functional interaction between KHDC1B and mCPEB1. Finally, KHDC1B levels and binding partners were shown to fluctuate with the cell cycle. KHDC1B, via its interaction with mCEPB1, may regulate translation of mRNA targets required for oocyte maturation.