Microplastics (MPs) and perfluorooctane sulfonate (PFOS) are emerging pollutants that are ubiquitously present in the environment and can cause series of ecotoxicological effects on aquatic animals. This study examined how the expression of genes related to insulin growth factor (igf1, igf2a, igf2b, igfra, and igfrb) and growth hormone (ghrh, gh1, ghra, and ghrb) changes during the development of zebrafish embryos exposed to 8 μm polyethylene microplastics (PE-MPs) and perfluorooctane sulfonate (PFOS) individually and in combination for 72 h. Our findings revealed that both low-concentrations of MP (50 μg/L) and PFOS (0.02 μg/L) treatments could significantly activate gene expression within a short period. High concentrations of MPs (500 μg/L) and PFOS (0.1 μg/L) not only rapidly activated gene expression but also sustained high expression levels for a longer duration. During combined exposures, peak gene expression in the low concentration groups (50 μg/L MPs and 0.02 μg/L PFOS; 50 μg/L MPs and 0.1 μg/L PFOS) primarily occurred within 12 h after treatment. In the high concentration groups (500 μg/L MPs and 0.02 μg/L PFOS), peak expression was also observed within 12 h. Notably, the combined exposure groups exhibited more pronounced effects on gene expression than the individual exposure groups. The activation of gene expression was both more significant and longer-lasting in the combined exposure, indicating a synergistic regulatory effect of MPs and PFOS. Overall, our study suggests that zebrafish embryo development can be significantly impacted by exposure to MPs, PFOS, and their combination, with combined exposures having a more lasting and profound effect on gene regulation compared to single exposures.