Updated project metadata. Insomnia is an economic burden and public health problem. This study aimed to explore potential biological pathways and protein networks for insomnia characterized by wakefulness after sleep. Proteomics analysis was performed in the insomnia group with wakefulness and the control group. The differentially expressed proteins (DEPs) were enriched, then hub proteins were identified by protein-protein interaction (PPI) network and verified by parallel reaction monitoring (PRM). Compared with the control group, the sleep time and efficiency of insomnia patients were decreased, awakening time and numbers after sleep onset were significantly increased (P < 0.001).