Hemidesmosomes are epithelial-specific attachment structures that maintain tissue integrity and resist tension. Despite their importance, how hemidesmosomes are regulated at the post-transcriptional level is poorly understood. <i>C. elegans</i> hemidesmosomes (CeHDs) share similar structure and composition with their mammalian counterparts, making <i>C. elegans</i> an ideal model for studying hemidesmosomes. Here we focus on the transcription regulator CCAR-1, identified in a previous genetic screen searching for enhancers of mutations in the conserved hemidesmosome component, VAB-10A/Plectin. Loss of CCAR-1 function in a <i>
vab-10(
e698)</i> background results in CeHD disruption and muscle detachment from the epidermis. CCAR-1 regulates CeHD biogenesis, not by controlling the transcription of CeHD-related genes, but by affecting the alternative splicing of <i>
unc-52</i>/Perlecan, the predicted basement ECM ligand of CeHDs. CCAR-1 physically interacts with HRP-2/hnRNPR, a splicing factor known to mediate <i>
unc-52</i> alternative splicing to control the proportions of different UNC-52 isoforms and stabilize CeHDs. Our discovery underlines the importance of post-transcriptional regulation in hemidesmosome reorganization. It also uncovers previously unappreciated roles of CCAR-1 in alternative splicing and hemidesmosome biogenesis, shedding new light on the mechanisms of mammalian CCAR1 function in tumorigenesis.