The current study aims to further delineate the associations between the synaptotagmin-like 3 (SYTL3) and solute carrier family 22 member 3 (SLC22A3) single-nucleotide polymorphisms (SNPs) and their haplotypes and gene–gene (G × G)/environment (G × E) interactions on the risk of hyperlipidemia (HLP) in the Maonan and Han ethnic groups. This evidence concerns the gene SYTL3 and hyperlipidemia.