This study aims to investigate the potential role of CYP2D6*10 (c.100 C>T) gene polymorphism in renal function injury among hypertensive patients without elevated cystatin C. A cohort of hypertensive patients without elevated cystatin C was enrolled between 2021 and 2024 in the Fourth Affiliated Hospital of Soochow University, and their peripheral venous blood was used for total RNA extraction and CYP2D6*10 genotype analysis. Based on kidney injury status, patients were categorized into two groups, hypertensive patients with kidney injury (n = 94) and those without (n = 893). General characteristics such as age, gender and hyperlipemia were compared between the two groups. Multiple genotype models were investigated between the two groups, including allele models, dominant models, recessive models, co-dominant models, and super-dominant models. The results revealed that in the co-dominant gene model (CC vs. CT vs. TT), the risk of hypertension combined with renal injury was lower with the CT genotype compared to the CC genotype (Odds Ratio (OR) = 0.55, 95% Confidence Interval (CI) = 0.32-0.93, p = 0.02). In the overdominance model (CC + TT vs. CT), the risk of hypertension and renal injury in CC and CT genotypes was 0.42 times lower than that in the CT genotype (OR = 0.42, 95% CI = 0.27-0.64, p < 0.001). This study proposes CYP2D610 gene polymorphism as a potential predictor of renal function injury in hypertensive patients with normal cystatin C levels.