Aim To study the relationship between vascular cognitive impairment (VCI) degree and serum inflammatory factors in patients with cognitive dysfunction of hypertensive cerebral small vessel disease (CSVD). Methods The clinical data of 141 patients with hypertension CSVD who were treated in Affiliated Hospital of Chengde Medical College from January 2016 to October 2018 were retrospectively analyzed. Patients were divided into non-VCI (WVCI) group (n＝45), vascular cognitive impairment no dementia (VCIND) group (n＝56) and vascular dementia (VD) group (n＝40) according to the degree of VCI. The levels of serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and plasma homocysteine (Hcy) were compared among the three groups, and the above indexes before and after treatment were compared in VCIND group and VD group. Furthermore, taking whether CSVD merges VCI as dependent variable, indicators with statistical differences in univariate analysis as independent variables, multivariate Logistic regression analysis was performed. Results The levels of serum hs-CRP, IL-6, IL-1β and TNF-α in the VCIND group and the VD group were significantly higher than those in the WVCI group (P＜0.05), and the levels of above serum indexes in the VD group were significantly higher than those in the VCIND group (P＜0.05). Compared with before treatment, the levels of serum hs-CRP, IL-6, IL-1β and TNF-α in VCIND group and VD group decreased significantly after treatment (P＜0.05 or P＜0.01). The levels of serum ICAM-1 and plasma Hcy in the VCIND group and the VD group were significantly higher than those in the WVCI group (P＜0.01), while the levels of serum ICAM-1 and plasma Hcy in the VD group were significantly higher than those in the VCIND group (P＜0.05). Compared with before treatment, the levels of serum ICAM-1 and plasma Hcy in VCIND group and VD group significantly decreased after treatment (P＜0.01). The levels of serum IL-6, IL-1β, TNF-α, ICAM-1 and plasma Hcy were negatively correlated with Montreal Cognitive Assessment Score (P＜0.05). Logistic regression analysis showed that serum IL-6, IL-1β, TNF-α, ICAM-1 and plasma Hcy were independent risk factors for VCI. Conclusion Inflammatory factors such as IL-6, IL-1β and TNF-α are involved in the occurrence of cognitive dysfunction in patients with hypertension CSVD, and the higher the levels, the more serious the degree of VCI.