In our study, STXBP6 was significantly hypermethylated and downregulated in most of the tumor samples, and the hypermethylation ratios of CpG units 3, 6, and 7 in STXBP6 were closely associated with patient age, tumor size, and tumor stage, respectively, suggesting that abnormal methylation in these CpG units of the STXBP6 promoter might serve as novel methylation markers for diagnosis of lung cancer in Xuanwei. Here, STXBP6 is linked to lung cancer.