Deciphering the mechanism of secondary cell wall/SCW formation in vascular plants is key to understanding their development and the molecular basis of biomass recalcitrance. A sophisticated network of transcription factors has been implicated in SCW synthesis in plants, but little is known about the implication of RNA-binding proteins in this process. Here we report that two RNA-binding proteins homologous to the animal translational regulator Musashi, Musashi-Like2/MSIL2 and Musashi-Like4/MSIL4, function redundantly to control SCW formation in interfascicular fibers and the setting of biomass recalcitrance. We show that the disruption of MSIL2/4 decreases the abundance of lignin in fibers and triggers an hypermethylation of glucuronoxylan that is linked to an over-accumulation of GlucuronoXylan Methyltransferase1/3 (GXM1/3) proteins. We demonstrate that MSIL4 binds to the GXM1/3 mRNAs, likely repressing their translation in wild-type plants. Our results reveal cell-type-specific mechanisms underlying SCW formation in Arabidopsis and point to a novel aspect of SCW regulation linking translational repression to regulation of glucuronoxylan methylation.