BackgroundSpiders generally exhibit robust starvation resistance, with hunting spiders, represented byHeteropoda venatoria, being particularly outstanding in this regard. Given the challenges posed by climate change and habitat fragmentation, understanding how spiders adjust their physiology and behavior to adapt to the uncertainty of food resources is crucial for predicting ecosystem responses and adaptability.ResultsWe sequenced the genome ofH. venatoriaand, through comparative genomic analysis, discovered significant expansions in gene families related to lipid metabolism, such as cytochrome P450 and steroid hormone biosynthesis genes. We also systematically analyzed the gene expression characteristics ofH. venatoriaat different starvation resistance stages and found that the fat body plays a crucial role during starvation in spiders. This study indicates that during the early stages of starvation,H. venatoriarelies on glucose metabolism to meet its energy demands. In the middle stage, gene expression stabilizes, whereas in the late stage of starvation, pathways for fatty acid metabolism and protein degradation are significantly activated, and autophagy is increased, serving as a survival strategy under extreme starvation. Additionally, analysis of expanded P450 gene families revealed thatH. venatoriahas many duplicated CYP3 clan genes that are highly expressed in the fat body, which may help maintain a low-energy metabolic state, allowingH. venatoriato endure longer periods of starvation. We also observed that the motifs of P450 families inH. venatoriaare less conserved than those in insects, which may be related to the greater polymorphism of spider genomes.ConclusionsThis research not only provides important genetic and transcriptomic evidence for understanding the starvation mechanisms of spiders but also offers new insights into the adaptive evolution of arthropods.