Five known members of the family of KH-domain poly(C)-binding proteins (Pcbp1-4, hnRNP-K) have an unusually broad spectrum of cellular functions that include regulation of gene transcription, regulation of pre-mRNA processing, splicing, mRNA stability, translational silencing and enhancement, the control of iron turnover, and many others. Mechanistically, these proteins act via nucleic acid binding and protein-protein interactions. Through performing these multiple tasks, the KH-domain poly(C)-binding family members are involved in a wide variety of biological processes such as embryonic development, cell differentiation, and cancer. Deregulation of KH-domain protein expression is frequently associated with severe developmental defects and neoplasia. This review summarizes progress in studies of the KH-domain proteins made over past two decades. The review also reports our recent finding implying an involvement of the KH-factor Pcbp1 into control of transition from naïve to primed pluripotency cell state.