 Oxidative stress can cause damage to cells by generating reactive lipid molecules called 4-hydroxanoneenol, 4-HNE. These molecules can modify proteins, DNA, and phospholipids, leading to cellular dysfunction and disease. Recently, research has focused on the role of mitochondria in the production of 4-HNE, which is generated from oxidized cardiolipin, a specific type of phospholipid found in mitochondria. This review summarizes the current understanding of how 4-HNE affects mitochondria and its implications for cancer development. This article was authored by Huqin Zhong and Huiyong Ng.