Exposure of humans to low levels of environmental oxygen results in alveolar hypoxia and normally causes chronic pulmonary hypertension and morphological alterations of precapillary pulmonary vessels. In this study, the microarray dataset GSE11341 was used to identify potential differentially expressed genes related with human lung microvascular endothelial cell hypoxia. In addition, gene ontology term enrichment analysis was performed to explore their underlying functions. In addition, we also investigated the small molecules by comparing with the Connectivity Map. We found that hypoxia samples of 3, 24, and 48 h relative to 0 h displayed 22, 21, and 29 differentially expressed genes, respectively. Among them, six genes (ADM, HMOX1, VEGFA, EGLN3, APOLD1, and ANGPTL4) were closely related to pulmonary microvascular endothelial cell hypoxia response. Three drugs (pindolol, sulfapyridine, and ciclopirox) were selected as candidates to treat hypoxia-related pulmonary diseases. In conclusion, our results provide some underlying drug targets for treatment of hypoxic pulmonary patients.