Pituitary adenoma is a typical adult primary brain tumor and 35% of pituitary adenomas are invasive. The enhancement of angiogenesis is essential for the spread and invasiveness of invasive pituitary adenoma. Thus, it is urgent to uncover the mechanism and relevant biomolecular targets for the therapy and prognosis of pituitary adenomas. The HP75 cells were transfected with si‑NC, si‑TFF3, pcDNA, and pcDNA‑TFF3 to investigate the effects of TFF3 on the proliferation, migration and invasion of pituitary tumor cell. The protein level of TFF3 and HIF‑1α/VEGFA was determined by western blot. The transwell migration assay and wound healing assay were used to investigate the influence of TFF3 on the cell migration and invasion of HP75 cells. The tumor angiogenesis was determined by tube formation assay. The proliferation of HP75 cells was assessed by using MTT assay and colony‑forming unit assay. The cell proliferation rate was separately enhanced and reduced remarkably in TFF3 overexpression group and si‑TFF3 group. TFF3 could modulate the proliferation, migration and invasion ability of HP75 cells. Furthermore, TFF3 may play a oncogenic role in HP75 cells. Overexpression of TFF3 enhanced the number of branching points and network formation in HP75 cells, suggesting the TFF3 had positive effects on cell angiogenesis. These results also disclosed a novel relationship between TFF3 expression and the activation of the HIF‑1α/VEGFA signaling pathway. In summary, this study uncovered new insight into the mechanisms of TFF3's anti‑tumor activities in pituitary adenoma cells by investigating its effects on HIF‑1α/VEGFA signaling pathway regulation.