Overcoming chemotherapy resistance is a major task for an effective anti-tumor treatment. Previous studies indicate that hypoxic tumor conditions and the hypoxia-inducible factor (HIF)-1a may affect chemotherapy resistance. Treating HeLa cells with the oxoglutarat analogue DMOG, which results in stabilization of HIF-1a in normoxia by inhibiting prolyl-4-hydroxlase domain (PHD) enzyme activity, induced chemotherapy resistance towards treatment with etoposide but not carboplatin. This effect was specifically dependent on PHD and HIF-1a since etoposide resistance was also observed in a tetracycline inducible PHD2 knock down cell line, as well as in DMOG-treated MEF HIF-1a+/+ cells but not in DMOG-treated MEF HIF-1a-/- cells. Etoposide resistance correlated with increased expression of MDR1 RNA as well as DMOG-inducible MDR-1 efflux activity (determined with the fluorescent dye DiOC2) in MEF HIF-1a+/+ cells.