Objective To study the effect of hypoxia-inducible factor 1α (HIF-1α) on microglia M1 polarization and its mechanism. Methods Microglia (BV-2 cells) were randomly divided into six groups: control, 10, 50, 100, 200 and 500 μg / L recombinant HIF-1α groups. Morphological changes of BV-2 cells were observed by fluorescence confocal microscopy. Changes of nuclear factor (NF)-κB p65, p-STAT1 and TRAF6 protein contents after recombinant HIF-1α protein stimulation were quantitatively analyzed by Western blot. Results Compared with the control group, microglia cells stimulated by recombinant HIF-1α protein became larger, round or phagocytic, and their processes became thicker and shorter. Intracellular NF-κB p65 and TRAF6 proteins were significantly increased compared with the control group, and the result of groups with varying concentrations of recombinant HIF-1α protein stimulation were significantly different. Conclusions HIF-1α can stimulate microglial M1 polarization and there was a dose-effect relationship between different concentrations of recombinant HIF-1α, which may be related to the regulation of TRAF6 and NF-κB activation through the TLR4 / Myd88 / NF-κB pathway.