Background Quantitative susceptibility mapping (QSM) can study the susceptibility values of brain tissue which allows for noninvasive examination of local brain iron levels in both normal and pathological conditions. Purpose Our study compares brain iron deposition in gray matter (GM) nuclei between cerebral small vessel disease (CSVD) patients and healthy controls (HCs), exploring factors that affect iron deposition and cognitive function. Materials and methods A total of 321 subjects were enrolled in this study. All subjects had cognitive examination including the Stroop color word test (SCWT) and MRI including multiecho gradient echo (mGRE) sequence. The patients with CSVD were divided into mild to moderate group (CSVD-M, total CSVD score <= 1) and severe group (CSVD-S, total CSVD score > 1). Morphology-enabled dipole inversion with an automated uniform cerebrospinal fluid zero reference algorithm (MEDI + 0) was used to generate brain QSM maps from mGRE data. Deep gray regional susceptibility values and cognitive function were compared among three groups (CSVD-S, CSVD-M, and HC) using multiple linear regression analysis and mediation effect analysis. Results There were significant differences in the SCWT scores and mean susceptibility values of the globus pallidus (GP), putamen (Put), and caudate nucleus (CN) among the three groups (P < 0.05, FDR correction). Age had a significant positive impact on the susceptibility values of GP (p = 0.018), Put (p < 0.001), and CN (p < 0.001). A history of diabetes had a significant positive influence on the susceptibility values of Put (p = 0.011) and CN (p < 0.001). A smoking history had a significant positive association with the susceptibility values of CN (p = 0.019). Mediation effect analysis demonstrated that iron deposition in the neostriatum partially mediated the relationship between hypertension and cognitive function. Age, diabetes, and smoking may increase iron deposition in the basal ganglia, associated with cognitive decline. The mean susceptibility values of the neostriatum played a mediating role in the association between hypertension and cognitive scores. Conclusions Age, diabetes, and smoking are associated with increased iron deposition in the basal ganglia and also linked to cognitive decline. This can help with understanding CSVD and its prevention and treatment.