Sexual dimorphism is common across the animal kingdom. Knowledge of the mechanisms of sexual size dimorphism is limited although it is important in biology and aquaculture. Tilapia is the common name for ~ 100 species of cichlid fish. Some are important aquaculture species and males outgrow females. To gain novel insights into the mechanisms underlying sexual size dimorphism, we analyzed the differences of brain transcriptomes between males and females in Mozambique tilapia and studied the function of the pro-opiomelanocortin (Pomc) gene in tilapia and zebrafish. The transcriptome analysis identified 123, 55, and 2706 sex-biased genes at 5, 30, and 90 dph (days post-hatch), respectively, indicating sexual dimorphism of gene expressions in the brain. The expression of Pomc in the tilapia brain was a female-biased at 30, 90, and 120 dph. An analysis of the DNA sequence located upstream of the tilapia Pomc transcriptional start site identified two estrogenic response elements. In vitro luciferase assay of the two elements revealed that β-estradiol significantly enhanced the expression of luciferase activity, suggesting that the expression of Pomc is mediated by estrogen. We knocked out Pomc in zebrafish using Crispr/Cas-9. The Pomc-knockout zebrafish showed faster growth and higher sensitivity to feeding as compared to the wild-type fish. Taken together, our results indicate that Pomc contributes to sexual size dimorphism and suggest that the high estrogen level in females promotes the expression of Pomc and suppresses feeding in female tilapias, which leads to the slower growth of female tilapias.