gpr98 is associated with a variety of diseases, and it is highly conserved in human and zebrafish. Constructing the gpr98 gene mutant strain of zebrafish can provide an excellent animal model and research basis for explaining the function of the gpr98 gene. In this paper, two target sites with a distance of 42 bp in exon 2 of zebrafish gpr98 gene were selected for sgRNA recognition. SgRNA was synthesized in vitro and co-injected with Cas9 mRNA into the embryo of zebrafish at 1-cell stage. A few partial embryos were randomly selected for DNA genotyping when they are in 72-hour stage. The results showed that in addition to the wild-type DNA bands, some embryos have a band smaller than the wild-type DNA bands. The F0 positive individuals were mated with wild-type zebrafish, and the offspring of the F0 generation positive individuals were tested for genotyping, and a stable genetic mutation strain with a deletion of 48 bp was obtained. The construction of the mutants model lays an important foundation for the study of the role of gpr98 gene in the development of cardiovascular, skeletal and other tissues and organs as well as the occurrence of related diseases.