BACKGROUND: Circadian Syndrome (CircS) is a significant marker of metabolic imbalance and has been linked to various chronic diseases. However, its relationship with cancer risk remains underexplored. This research aims to explore the relationship between CircS and cancer, while also assessing the possible mediating role of the triglyceride glucose (TyG) index. METHODS: Baseline data from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and follow-up data from 2015 were analyzed, including participants' sociodemographic characteristics, health behaviors, and metabolic indicators. Linear regression, mediation analysis, and logistic regression were employed to explore relationships between CircS, cancer risk, and the TyG index, with a dose-response analysis conducted on TyG index and cancer risk. RESULTS: Among 7,864 middle-aged and elderly participants, CircS was significantly and positively associated with cancer risk (r = 0.17, P <
0.001). The TyG index showed a significant correlation with both CircS (r = 0.52, P <
0.001) and cancer (r = 0.15, P <
0.001). Mediation modeling indicated that the TyG index partially mediated the association between CircS and cancer, accounting for 23% of this relationship. Additionally, a significant nonlinear dose-response relationship was observed between the TyG index and cancer risk (P CONCLUSION: Circadian syndrome is associated with increased cancer risk, with the TyG index partially mediating this relationship.