Objective：To investigate the effects and mechanisms of netrin-1（NTN1）in antagonizing polychlorinated biphenyls（PCBs）toxicity in retinal ganglion cells RGC-5. Method：RT-qPCR and Western blot were used to detect the expression levels of NTN1 and ERK signaling molecules in RGC-5 cells after exposure to PCB1254；NTN1 small interfering RNA and NTN1 overexpression lentivirus were used to transfect RGC-5 cells，and control groups were set as negative control group and empty lentivirus group，and treated with or without PCB1254. Cell proliferation was detected by CCK-8 assay，cell cycle and apoptosis were detected by flow cytometry，and expression levels of ERK signal molecules were detected by RT-qPCR and Western blot. Results：①After exposure to PCB1254，the expression levels of NTN1 and p-ERK in RGC-5 cells were significantly reduced. ②NTN1 silencing reduced RGC-5 cell proliferation and led to S phase arrest；NTN1 silencing significantly inhibited the phosphorylation of ERK signaling molecules. ③NTN1 overexpression rescued the proliferation of RGC-5 cells after PCB1254 exposure，reduced the proportion of S phase cells，and increased the phosphorylation level of ERK. Conclusion：NTN1 can regulate the ERK signaling pathway to antagonize the decline in the proliferation of retinal ganglion cells caused by PCB1254 exposure，reduce the proportion of S-phase cells，and alleviate the toxic effects of PCB1254 on retinal development.