Background <p>Sleep disturbances have increasingly been linked to dysregulation of the immune-inflammatory system. However, evidence regarding such alterations in patients with chronic insomnia disorder (CID) remains limited. This study aimed to characterize the inflammatory cytokine profile of CID and to investigate its association with subjective sleep quality.</p> Methods <p>Thirty-two patients with CID were recruited from the Sleep Medicine Center at the First Affiliated Hospital of Jinan University between January 2024 and June 2025, along with 31 community-recruited healthy controls. Depressive symptoms, anxiety symptoms, and subjective sleep quality were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and Pittsburgh Sleep Quality Index (PSQI), respectively. Serum levels of IL-1β, CRP, IL-6, IL-8, IFN-γ, TNF-α, and IL-10 were measured using enzyme-linked immunosorbent assay (ELISA). Finally, Spearman correlation and receiver operating characteristic (ROC) analyses were performed.</p> Results <p>Compared with healthy controls, patients with CID had higher IL-1β and IFN-γ levels and lower IL-10 levels (all <i>P</i> &lt; 0.05). IL-1β levels were positively correlated with the PSQI total score (<i>r</i> = 0.429, <i>P</i> = 0.003), whereas IL-10 levels were negatively correlated with the PSQI total score (<i>r</i> = − 0.540, <i>P</i> = 0.013). ROC analyses showed that IL-1β alone (AUC = 0.752; 95% CI: 0.635–0.869; <i>P</i> &lt; 0.001) and a combined model incorporating IL-1β, IFN-γ, and IL-10 (AUC = 0.752; 95% CI: 0.637–0.867; <i>P</i> &lt; 0.001) had comparable discriminative performance for CID.</p> Conclusions <p>Patients with CID exhibit altered inflammatory cytokine levels, and some of these alterations were associated with subjective sleep quality, suggesting that immune–inflammatory dysregulation may be involved in the pathophysiology of CID.</p> Clinical trial number <p>Not applicable.</p>