Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Young children are commonly exposed to these chemicals via ingestion of settled dust. Several PFAS have been associated with cancers in adults, yet little is known about the risk in children. We investigated whether PFAS concentrations in residential dust were associated with childhood acute lymphoblastic leukemia (ALL). Vacuum bags were collected in homes of 178 children diagnosed with ALL and 204 healthy controls (age 0-7 years) residing in California (2001-2007). Dust samples were sieved and analyzed for 19 PFAS using targeted liquid chromatography mass spectrometry analysis. The effects of individual PFAS and PFAS mixtures were estimated for eight PFAS with at least 50% above the limit of quantification (LOQ) using logistic regression, G-computation, and generalized additive modeling (GAM). In the model mutually adjusting for eight PFAS, a statistically significant association was seen only for N-ethyl perfluorooctane sulfonamido acetic acid (EtFOSAA) (OR