Fine particulate matter (PM₂.₅) has been associated in humans with inflammation, oxidative stress and cancer. Studies had shown that curcumin could potentially inhibit these effects; however, there had been no in vivo or in vitro reports about the effects of curcumin on organisms exposed to PM₂.₅. This predictive study explored the possible biological functions and pathways involved in the mechanism of curcumin inhibition of the hazardous effects of PM₂.₅. For predictive analysis, microarray data were used to investigate the effect of PM₂.₅ on human bronchial epithelial cells (HBEC), and human target proteins of curcumin were retrieved from PubChem. Two protein-protein interaction (PPI) networks were established based upon differential genes and target proteins, respectively, and the common network of these two networks was found. Functional and pathway analysis of the common network was performed using the Ingenuity Pathways Analysis (IPA) software. The results suggested that the predictive effects of curcumin on HBEC exposed to PM₂.₅ were involved in bio-functions, including inflammatory response of airway, cancerogenesis, and apoptosis, and in pathways such as cancer, glucocorticoid receptor signaling, and NF-kappaB signaling. This study predicted for the first time that curcumin could be a potential therapeutic agent for protecting the human airway from the hazardous effects of PM₂.₅.