Abstract: Objective To investigate the expression and clinical significance of p15 and SOCS1 methylation in myelodysplastic syndrome. Methods We examined 67 MDS patients (39 male and 28 female) with the median age of 59 years (21-83). Of them, 34 cases were the relatively low risk groups (low-risk 6 cases, intermediate-Ⅰ 28 cases), 33 cases were the relatively high risk groups (intermediate-Ⅱ 16 cases, high risk 17 cases). Methylation-specific PCR (MSP) was used to detect the methylation of the above two genes in 67 patients with MDS and 18 patients with iron deficiency anemia as controls, to analyze the relationship between p15 and SOCS1 methylation and the clinical indexes. Results The methylation rates of p15 and SOCS1 were 37.3% and 47.8% in 67 MDS patients, while 0% and 5.6% in the control group (P<0.05). The methylation of p15 and SOCS1 were correlated with different clinical indexes, but both increased along with the increase of International Prognostic Scoring System (IPSS) scores (P<0.05). The median overall survival of patients with p15 methylation were 8(95% CI:5.2-10.8) months, which was significant different with that of the patients without methylation 26 (95% CI:15.8-36.2) months (P< 0.05). The median overall survival of patients with SOCS1 methylation were 7(95% CI:5.0 -9.1) months, which was significant different with that of the patients without methylation 26(95% CI:18.2-33.8) months (P<0.05). Patients with 2 genes methylation had shorter survival time in all patients, the relatively low risk groups and the relatively high risk groups (P<0.05). In multivariate analysis, p15 and SOCS1 remained negative prognostic factors. Conclusion The methylation of p15 and SOCS1 were independent prognostic factors for overall survival in MDS.