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Vitamin D plays an important pleiotropic role in maintaining global homeostasis of the human body. Its functions go far beyond skeletal health, playing a crucial role in a plethora of cellular functions, as well as in extraskeletal health, ensuring the proper functioning of multiple human organs, including the skin. Genes from the Grainyhead-like (<i>GRHL</i>) family code for transcription factors necessary for the development and maintenance of various epithelia. Even though they are involved in many processes regulated by vitamin D, a direct link between vitamin D-mediated cellular pathways and <i>GRHL</i> genes has never been described. We employed various bioinformatic methods, quantitative real-time PCR, chromatin immunoprecipitation, reporter gene assays, and calcitriol treatments to investigate this issue. We report that the vitamin D receptor (VDR) binds to a regulatory region of the Grainyhead-like 1 (<i>GRHL1)</i> gene and regulates its expression. Ectopic expression of VDR and treatment with calcitriol alters the expression of the <i>GRHL1</i> gene. The evidence presented here indicates a role of VDR in the regulation of expression of <i>GRHL1</i> and correspondingly a role of <i>GRHL1</i> in mediating the actions of vitamin D.