In many countries the hypomethylating agents (HMAs) are the major compounds to treat patients suffering from myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with low bone marrow blast counts. The elderly AML patients with poor performance status and comorbidity also benefit from HMAs. Patients who resist to HMA have a poorer outcome as compared to sensitive patients. Therefore, the reliable markers for predicting response to HMAs are urgeatly needed in clinic. In this review, the biomarkers for predicting response of patients with MDS or AML to HMAs are summarized.