OBJECTIVES: The relationship between C-reactive protein (CRP) and the risk of developing kidney stones is unclear, and we aimed to assess the association between CRP and kidney stones in US adults. METHODS: We used data from NHANES 2007-2010, and we excluded participants who were under 18 years of age and lacked data on CRP and kidney stones. Finally, we included a total of 11,033 participants and performed weighted multivariate regression analysis and subgroup analysis to assess the independent relationship between CRP and kidney stones. RESULTS: The mean prevalence of kidney stones among the participants was 9.8%. Notably, as CRP levels increased, the prevalence of kidney stones exhibited a corresponding rise across quartiles (Kidney stones: Quartile 1: 7.59%; Quartile 2: 8.77%; Quartile 3: 9.64%; Quartile 4: 10.89%). CRP was positively associated with the risk of kidney stones (Model 1: OR = 1.09, 95% CI: 1.01-1.18, p = 0.03; Model 2: OR = 1.09, 95% CI: 1.00-1.18, p = 0.03, Model 3: OR = 1.14, 95%CI: 1.02-1.26, p = 0.04). Participants in the highest CRP quartile experienced a 69% increased risk of kidney stones compared to those in the lowest quartile (OR = 1.64, 95% CI: 1.04-2.59, p = 0.03). Notably, interaction tests revealed that gender, BMI, diabetes, hypertension, CKD and smoking or alcohol consumption status did not significantly influence the association between CRP and kidney stones. CONCLUSIONS: Our findings reveal a significant association between higher CRP levels and an increased risk of kidney stones. In clinical practice, heightened awareness of CRP as a potential biomarker could aid in risk assessment and management strategies for kidney stone patients.