Silica nanoparticles induced reproductive toxicity, but its mechanism is unknown.To investigate toxic mechanism of SiNPs, 60 male mice were randomly divided into three groups:control group, saline group and SiNPs group, with two evaluation time points (45 and 75 days after the first dose) per group.Mice in SiNPs group were treated with SiNPs at dose of 2.0mg/kg every three days, total 15 times for 45 days, and mice in saline group were given the same volume of physiological saline, and control group were treated with nothing.Then half of mice in each group were sacrificed for tissue samples on days 45 and 75.In vitro, GC-2spd cells were exposed to various concentrations of SiNPs for 24h.Results showed that SiNPs down-regulated expressions of Sohlh 1/Cyclin A1/Cyclin B1/CDK 1/CDK 2, led to decreases both number of spermatogenic cells and diameter of seminiferous tubules, caused damages of seminiferous epithelium, and significantly improved ROS in testicular tissue of mice on day 45, while these changes all recovered on day 75.In vitro, SiNPs induced G0/G1 phase cycle arrest and proliferation inhibition, due to decrease of cell viability and DNA damages of GC-2spd cells.The results suggested that SiNPs might induce cell cycle arrest and proliferation inhibition by down-regulating expressions of meiotic regulators through causing DNA damages resulting from oxidative stress, lead to inhibition of the start and process of meiosis, therefore decreased sperm quantity.And the damages of male reproductive system caused by SiNPs may be reversible.