["Autism Research, EarlyView. ", "\nABSTRACT\nFyn‐related kinase (FRK), which belongs to the Src family of non‐receptor protein tyrosine kinases, functions during the cell cycle. Here, we report an autistic patient with an intragenic mutation of FRK and two other autism‐related genes. Circumventing the barrier of murine model studies, we generated the CRISPR/Cas9‐engineered frk−/− zebrafish. We found that frk‐knockout led to early developmental abnormalities. Frk−/− fish exhibited autism‐like behavior, including impaired social communication, repetitive stereotypic behavior, altered anxiety level, and cognitive dysfunction in both larvae and adults, which could be rescued by the transgenic neuron‐specific re‐expression of frk. GO and KEGG analysis of RNA‐sequencing data found that the frk‐knockout‐induced DEGs were mainly concentrated in processes and functions related to cell metabolism. PPI network analysis of the detected DEGs suggested that the cyp24a1/tp53 pathway may play a key role in frk‐knockout‐induced autism. Furthermore, we found that the numbers of BrdU+ cells were significantly increased in the frk−/− larval brains. Inhibition of Cyp24a1 or activation of tp53 reduced cell proliferation and partially ameliorated social impairments in frk−/− zebrafish. Overall, our work established an autism model of frk‐knockout with an assessable behavior phenotype in zebrafish and provided key insights into cell proliferation and the influence of the cyp24a1/tp53 pathway‐regulated cell proliferation on frk‐knockout‐induced autism‐like behaviors.\n"]