Pollutants such as PM2.5 are polluting the environment seriously, causing numerous health problems. However, the skin toxicity caused by PM2.5 has been little reported so far. CCK-8 was used to test the effects of PM2.5 on melanin cell proliferation. The effect of PM2.5 on melanocyte apoptosis was detected by flow cytometry. ELISA was used to detect the expression of oxidative stress-related factors, including reactive oxygen species (ROS). The expression of autophagosomes was detected by MDC immunohistochemical staining, and Western blot was used to detect the expression of autophagy marker LC3II/I. With the increasing concentrations of PM2.5, the proliferation rate and apoptosis rate of melanocytes decreased significantly, meanwhile the expression of oxidative stress-related factors ROS, was obviously increased. The expression of LC3II/I induced by PM2.5 venom was higher than that of the control group in a concentration-dependent manner. However, there was no statistically significant difference between the water-soluble components of PM2.5 and the water-insoluble ones. PM2.5 can inhibit the proliferation of melanocytes and induce their apoptosis, which may be related to the oxidative damage of PM2.5. PM2.5 also induced autophagy in melanocytes, which is obviously correlated with its concentration. The mechanism may be a self-protective response of cells to oxidative stress injury and apoptosis.