Gastric cancer is a common malignancy with high mortality and limited therapeutic options. Hypoxia inducible factor-1 α (HIF-1α) is the key responser adapted to tumor hypoxia. Under hypoxia conditions, HIF-1α signaling is activated and responsible for cell biology associated with metabolism, inflammation, vascular homeostasis and tumorigenesis. Activation of HIF-1α signaling has been observed in a series of cancers including gastric cancer. Moreover, a variety of oncogene products may be induced by HIF-1α expression. Pharmacologic manipulation of HIF-1α may provide a novel therapeutic approach to gastric cancer. In this review, we summarize the recent information on HIF-1α in gastric cancer with special focus on the mechanism underlying HIF-1α signaling effects on proliferation, apoptosis, angiogenesis, EMT and drug-resistance of cancer cells, thereby predicting new therapeutic agents for better management of this malignancy.