Chronic exposure to crystalline silica causes the development of silicosis, which is one of the most important occupational diseases worldwide. In the early stage of silicosis, inhaled silica crystals initiate oxidative stress, a cycle of persistent inflammation and lung injury. And it is crucial to prevent the deteriorative progression in the onset of the disease. Herein, we present a promising candidate for the treatment of crystalline silica-induced pulmonary inflammation, using a silicosis mouse model caused by intratracheal instillation based on local administration of β-alanine and hydroxyl functionalized C70 fullerene nanoparticles (FNs). The results demonstrate that FNs could significantly alleviate inflammatory cells infiltration, lower the secretion of pro-inflammatory cytokines, and reduce the destruction of lung architecture stimulated by crystalline silica. Further investigations reveal that FNs could effectively inhibit the activation of NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome, and thus prevent the secretion of mature IL-1β and neutrophil influx, deriving from the superior ROS scavenging capability. Importantly, FNs could not cause any obvious toxicity after pulmonary administration.