We herein investigated the possible association of the Hif-1α signaling pathway with response to 5-AZA therapy in MDS/AML patients. Our data demonstrated that 5- AZA-responders present with higher Hif-1α mRNA and protein expression compared to 5-AZA-non-responders/stable disease patients, before the initiation of therapy...Kaplan-Meier survival analysis revealed a significant correlation between high Hif-1α mRNA expression and better survival rates, while logistic regression analysis showed that Hif-1α mRNA expression is an independent predictor of response to 5-AZA therapy. Moreover, we found that 5-AZA-responders exhibited elevated mRNA levels of the Hif-1α downstream targets LDHa and BNIP3L, a further indication of an overactivated Hif-1a signaling pathway in these patients.