Dysregulation of the complement system has been linked to pathogenesis of hypertension. However, whether genetic changes of complement factor H (CFH) and its related genes are associated with hypertension is unknown. We genotyped three SNPs in the CFH gene cluster that are closely linked to age-related macular degeneration, namely rs1061170 (Y402H), rs2274700 (A473A) and rs7542235 (CFHR1-3Δ), and tested for their associations with blood pressure and hypertension risk in a population-based cohort including 3,210 unrelated Chinese Hans (50-70 years of age) from Beijing and Shanghai. We found that rs2274700 (A473A) and rs7542235 (CFHR1-3Δ) were both significantly associated with diastolic blood pressure (DBP) (β = 0.632-1.431, P≤0.038) and systolic blood pressure (SBP) (β = 1.567-4.445, P≤0.008), and rs2274700 (A473A) was associated with hypertension risk (OR [95%CI]: 1.175 [1.005-1.373], P = 0.048). Notably, the associations of rs2274700 (A473A) with DBP (P = 2.1×10(-3)), SBP (P = 8×10(-5)) and hypertension risk (P = 7.9×10(-3)) were significant only in the individuals with low CRP levels (<2.0 mg/l), but not in those with CRP levels ≥2.0 mg/l (P≥0.0807) (P for interaction ≤0.0467). However, no significant association between rs1061170 (Y402H) and blood pressure or hypertension risk was observed (P≥0.259). In conclusion, our results suggest that genetic variations in CFH and its related genes may contribute to hypertension risk in Chinese Hans.