Abstract: The term insomnia refers to the sleep defect or inability to sleep. A patient's disturbance of sleep to a considerable degree that interferes with day functioning is a main element to take into account of insomnia diagnosis. Cognitive dysfunction and dementia occurs because hypertension. HSP90 is bioactive marker for molecular helper and is related with a number of diseases like hypertension, diabetes and cancers. In this study, we focused to assess the Serum HSP90 in patients with insomnia, and to analyze any correlation with biochemical parameters studied. A case-referent study design included 120 Iraqi individuals, 60 of them suffered from insomnia (36 males and 24 females) against a group of 60 healthy individuals (36 males and 24 females) whose ages were similar to those of the patients aged (20-75) years. The serum HSP90 levels and metabolic parameters including BMI, WHR, SBP, DBP, MDA, AOPPs, 8-OHdG, Vitamin D, Iron, Serotonin, Dopamine, Melatonin and Cortisol were assessed in all individuals. The results were analyzed statistically to examine the differences between the groups and identify the relationship between the studied parameters. According to the statistical analysis, SBP was significantly elevated in insomnia group as compared to healthy referent group (140.50±14.0 versus 109.0±16.2, P=0.02), respectively. DBP was significantly elevated in insomnia group as compared to healthy referent group (90.5±10.62 versus 71.5±12.8, P=0.04), respectively. Serum HSP90 was significantly elevated in insomnia group as compared to healthy referent group (110±10 versus 60±5, P=0.04), respectively. Serum MDA was significantly elevated in insomnia group as compared to healthy referent group (5±0.93 versus 2±0.62, P= 0.01), respectively. Serum AOPPs was significantly elevated in insomnia group as compared to healthy referent group (221±45.1 versus 97.5±31.9, P=0.03), respectively. Serum 8-OHdG was significantly elevated in insomnia group as compared to healthy referent group (3.5±0.6 versus 1.25±0.28, P=0.02), respectively. No strong significant association was observed between HSP90 and other biochemical parameters studied, except SBP and DBP, while weak significant association was found with MDA, AOPPs and 8-OHdG. The current investigation found that insomnia patients had considerably higher levels of HSP90 than the control group. SBP and DBP have a strong positive association with HSP90 levels. These results suggest that HSP90 level in insomnia patients may act as a novel protective signal for the initial discovery of dementia in patients with insomnia.