SII-K1 is a member of the transcription elongation factor S-II family. In the mouse, SII-K1 is expressed exclusively in the liver, kidney, heart, and skeletal muscle. Here, we report that deletion of the SII-K1 gene in mice resulted in the downregulation of the synaptotagmin-like 1 (Sytl 1) gene in liver and of the coiled-coil domain-containing 21 (Ccdc21) gene in liver and kidney. Moreover, the induction of the metallothionein I (Mt I) gene in SII-K1-deficient mice liver was impaired in diethyl maleate-induced oxidative stress conditions. Our results suggest that SII-K1 regulates these genes in vivo.