Abstract: OBJECTIVE To study the transcriptome of multiple myeloma(MM) affected by hypoxia and obtain the differential expressed genes(DEGs), which facilitate the mechanism of cellular hypoxic resistance. METHODS The expression profile of MM cell lines cultured under hypoxia and CD38 positive cells derived from patient bone marrow was obtained from GEO database. The DEGs with high consistent under hypoxia were analyzed by Limma package. GO and KEGG analysis were performed on the DEGs. Additionally, the expression levels of the DEGs on MM patient survival were studied by TCGA database. Finally, the potential drugs against hypoxia were predicted by the DEGs. RESULTS Totally 28 consistent DEGs were selected from the two datasets, which involved in cell metabolism, mitochondrial structure, autophagy and etc. These DEGs might contribute to the pro-survival effect in MM under hypoxia. The high expression of ANXA1, CLU, DPYSL3, CEP128, DDIT4, HMGCS1 suggested poor prognosis in MM patients which shorten the survival periods. The CMAP analysis suggested that PARP inhibitors could be used as a hypoxic antagonist. CONCLUSION DEGs under hypoxia in MM were obtained by bioinformatic analysis, some of which indicated the poor prognosis in MM patients. This may be associated with the pro-survival effect of hypoxia in tumor cells. PARP inhibitors may be used to inhibit the negative effect of hypoxia and combined with other chemotherapeutic drugs to achieve better therapeutic effect in MM.