Background: Palm oil is an important feedstock for biofuel. Palm oil yield is seriously affected by drought stress. However, not much is known about the molecular responses of oil palm to drought stress.Results: We studied the root transcriptomic responses of oil palm seedlings under normal culture and 14-day drought stress using RNA-seq and bioinformatics analysis. We identified 1293 differentially expressed genes (DEGs), involved in several molecular processes, such as cell wall biogenesis and functions, phenylpropanoid biosynthesis and metabolisms, ion transport and homeostasis and cellular ketone metabolic process, as well as small molecule biosynthetic process. We observed that DEGs were significantly enriched into the two categories: hormone regulation and metabolism, as well as ABC transporters. In addition, we identified three protein-protein interaction networks involved in the response to drought stress, including ion transport, reactive nitrogen species metabolic process and nitrate assimilation. Finally, 96 differentially expressed transcription factors were detected to be associated with drought stress response, which were classified into 28 families.Conclusions : The transcriptomic responses of oil palm seedlings to drought stress were systematically analysed, revealing important genes, pathways, networks and transcription factors involved in drought stress responses. These results provide new insights into the mechanisms of drought stress responses in economic crops. The genes and pathways identified in this study provide valuable genomic resources to improve drought tolerance of oil palm by both genetic modification and selective breeding.