Background <p>Fine air particulates (PM2.5) are identified as a significant environmental factor contributing to the progression of non-small cell lung cancer (NSCLC). This study aims to explore the underlying mechanisms on PM2.5 and the biological behaviors of cancer cells.</p> Methods <p>By employing a series of the vitro assays, we assessed cell viability, invasion capacity and wound healing ability following the PM2.5 exposure. Additionally, gene expression profiling was conducted to identify potential key genes and pathways involved in this process.</p> Results <p>Our results demonstrated that to PM2.5 exposure enhances the migratory and invasive capabilities of NSCLC. The 126 eventful differentially expressed genes (DEGs) were identified by RNA-Seq in PM2.5-exposed H1299 cells. Meanwhile, according to the qRT-PCR, we found expression of these genes were similar to the trends in the RNA-Seq data.</p> Conclusions <p>These results provide novel insights into the role of PM2.5 in NSCLC prognosis and may pave the way for targeted therapeutic strategies.</p>