This study aimed to investigate the alteration of intracellular proteome of MCF-7 cells following membrane permeabilization by sumaCTX at increasing concentration, using a label-free quantitative (LFQ) approach. The secretome represents the leakage of intracellular proteins in MCF- 7 cells were subjected to trypsin digestion and LC-MS/MS. Based on the LFQ secretome, there was a total of 105 distinct abundance proteins (DAPs) identified in different experimental groups. Further bioinformatics analyses revealed that most of these DAPs were confined to cytoplasmic, nucleus, and membrane. The DEPs involved in metabolic pathways, membrane integrity, inflammatory responses, and necroptosis. There were relatively higher detectable levels of DAPs in the secretome treated with a higher concentration of sumaCTX, suggesting prominent membrane permeabilization. The necroptosis was possibly a stress response in MCF-7 upon exposure to the high concentration of sumaCTX.