Current understanding of ambient particulate matters (PM) health effects is restricted by their sources, time periods and component differences. Here, an eukaryote model organism Saccharomyces cerevisiae was used to study the differing cell level responses when exposed to 465 air samples collected from 31 Chinese cities across major latitudes. Results from cell-released volatile organic compounds (VOCs), transcriptome and proteome showed large variations in responses of the cells with the exposure. Gene and protein expression of S. cerevisiae with 3 hr PM exposure were mainly enriched in varying metabolism pathways. The genes significantly associated with VOCs are mostly enriched in six major KEGG groups, including cellular processes, genetic information processing, human diseases, metabolism, and organismal systems. Different PM components, including microbials, metal elements and organic compounds, are important players for the differences. This work also revealed the potential VOCs biomarkers for real-time monitoring PM health effects in vivo.