Epigenetic silencing of secreted frizzled-related protein (SFRP) genes, antagonists of the WNT pathway, contributes to the pathogenesis of several cancers including non-small cell lung cancer (NSCLC). We hypothesize that methylation analysis of SFRPs family could improve their use as a panel of biomarkers for diagnosing and staging of NSCLC in China. The expression of four SFRP members (SFRP1, 2, 4, and 5) in NSCLC samples was screened by RT-PCR and quantitative real-time PCR. Only SFRP1 was significantly downregulated in NSCLC, as compared to adjacent normal tissues and benign pulmonary disease tissues (P=0.006). Promoter hypermethylation of SFRP1 was found in 32.1% (25/78) NSCLC specimens and was closely correlated with loss of expression, besides SFRP1 hypermethylation was associated with lymph metastasis (P=0.039) and disease progression within one year (P=0.027). Furthermore, methylated SFRP1 was detected in 28.2% (22/78) of plasma samples from NSCLC patients while only 4% (2/50) in cancer-free controls, and the concordance of SFRP1 methylation status in tumor tissues and corresponding plasmas was satisfactory (P <0.001). In conclusion, epigenetic inactivation of SFRP1 is a common event contributing to lung carcinogenesis and maybe used as a potential biomarker for NSCLC in Chinese population.