The EGR1 protein encoded by early growth response factor 1 (egr1) belongs to the Cys2-His2 type zinc finger protein family. Previous studies have demonstrated its critical roles in animal growth, development, reproduction, and immune processes; however, its function in craniofacial development remains unreported. In this study, we utilized in situ hybridization to identify the specific expression of the egr1 gene in the head region of zebrafish during early cartilage development. To elucidate the function of EGR1 in this context, we employed CRISPR/Cas9 gene editing to generate egr1 knockout zebrafish and analyzed their phenotypes. Alcian blue staining revealed abnormalities in craniofacial cartilage development in egr1^–/– mutant embryos, including deformities in Meckel's cartilage and ceratohyal, as well as disarray in the opercular and branchial regions. Our findings demonstrated the critical impact of egr1 gene deficiency on early craniofacial cartilage development in zebrafish, offering valuable insights into the pathogenesis of cartilage-related diseases and potential therapeutic strategies.