There are many epidemiological studies asserting that fine dust causes lung cancer, but the biological mechanism is not clear. This study was conducted to investigate the effect of PM₁₀ (particulate matter less than 10 μm) on single nucleotide variants through whole genome sequencing in lung epithelial cancer cell lines (HCC-827, NCI-H358) that have been exposed to PM₁₀. The two cell lines were exposed to PM₁₀ for 15 days. We performed experimental and next generation sequencing analyses on experimental group that had been exposed to PM₁₀ as well as an unexposed control group. After exposure to PM₁₀, 3005 single nucleotide variants were newly identified in the NCI-H358 group, and 4402 mutations were identified in the HCC-827 group. We analyzed these single nucleotide variants with the Mutalisk program. We observed kataegis in chromosome 1 in NCI-H358 and chromosome 7 in HCC-827. In mutational signatures analysis, the COSMIC mutational signature 5 was highest in both HCC-827 and NCI-H358 groups, and each cosine similarity was 0.964 in HCC-827 and 0.979 in the NCI-H358 group. The etiology of COSMIC mutational signature 5 is unknown at present. Well-designed studies are needed to determine whether environmental factors, such as PM₁₀, cause COSMIC mutational signature 5.