Fatty acids are essential nutrients to maintain normal physiological functions in the body and need to be activated by relevant enzymes in the body before they enter the normal metabolic pathway. While dysregulation of fatty acid metabolism is closely associated with tumorigenesis. Long - chain acyl - CoA synthases ACSLs are responsible for the activation of long - chain fatty acids. The ACSLs family consists of five members ACSL1 ACSL3 ACSL4 ACSL5 and ACSL6 with different isoforms having different cellular localizations which can catalyze different lipids and influence their metabolic routes. ACSLs are extensively involved in endoplasmic reticulum stress iron death drug resistance and tumor inflammatory microenvironment by regulating fatty acid metabolism. And ACSLs are often deregulated in tumors and can affect fatty acid metabolism. However fatty acids can activate different ACSLs by activating multiple transcription factors in combination with gene response elements and tumor cells and protein ubiquitination can regulate the expression of ACSLs genes. This leads to the development of metabolic disorders in tumors and other metabolic diseases. Triacsin C an inhibitor of ACSLs has great potential for the development of antitumor drugs. This article reviews the expression and localization of ACSLs in cells physiological functions functions in tumors and molecular mechanisms. The results indicate that ACSLs are associated with inflammatory response lipid metabolism disorders tumor invasion and metastasis in tumors which are important for tumor development and may become valuable biomarkers and therapeutic targets for tumor therapy.