HIF1A and neoplasm: Overall, our results demonstrate that mitochondrial Ca2+ uptake is required for TNBC progression in vivo, and clarify the close correlation between mitochondrial Ca2+ uptake and mROS production, which targets the transcriptional regulation of HIF1A. According to our model, mitochondrial Ca2+ uptake prompts sustained mROS production and thus activation of a HIF‐1α signaling route that contributes to tumor growth and metastasis formation.