GPER agonist G-1 inhibited IL-6 and VEGF-A in TNBC cells. G-1 or anti-IL-6 suppressed in vitro tube formation of HUVECs. Recombinant IL-6 reversed inhibitory effects of G-1 on angiogenesis and migration. G-1 inhibited the binding of NF-κB with IL-6 promoter. The suppression of IL-6 by G-1 inhibited HIF-1α and STAT3 signals.