Researches had shown that SiNPs could damage seminiferous epithelium and reduce the quantity and quality of sperms, but little is known about the toxicity mechanism of SiNPs on male reproductive system.To investigate toxic mechanism of SiNPs, male germ cell lines (GC-2spd) were exposed to 0, 6.25, 12.5,25 or 50 μg / mL SiNPs for 24 h, respectively.The results showed that SiNPs resulted in a dose-dependent reduction in cell viability, as well as increases in the LDH release and cell apoptosis rate.SiNPs can lead to DNA strand breaks and abnormal mitosis.In addition, SiNPs induced cell cycle arrest in the G0/G1 phase and proliferation inhibition.SiNPs could simultaneously activate negative signaling pathway (PKC-δ/p53/p21cip1) by PKC-δ and positive signaling pathway (PKC-α/MAPK) by PKC-α.However the lower expressions of cyclin E and CDK2 indicated that negative signaling pathway mediated by PKC-δ played a dominant role in the process of cell cycle.Our results suggested that SiNPs might activate PKC-δ mediated negative signaling due to DNA strand breaks resulting from ROS.The activity PKC-δ mediated negative signaling arrested GC-2 cells at G0/G1 phase, resulting in abnormal mitosis and cell apoptosis.