In this study, we show evidence for autophagy’s key role in the modulation of the biological status of residual heat-treated BC cells as seen by: (1) BC cells surviving sublethal heat treatment through autophagy induction; (2) autophagy promoting the EMT of the residual BC cells by up-regulating the TGF-β2/Smad2 signaling; (3) the reciprocal interactions of autophagy and TGF- β2 promoted-EMT enhancing the invasion and migration capabilities of the residual BC cells in this process; and, (4) an autophagy inhibitor suppressing proliferation and increasing apoptosis of the residual BC cells. This evidence concerns the gene SMAD2 and breast cancer.