Objective To investigate the risk factors influencing the recurrence of calcium oxalate kidney stone. Methods The clinical data of patients with calcium oxalate kidney stone were collected; they were hospitalized in Changhai Hospital, Navy Medical University (Second Military Medical University) from Sep. 2015 to Dec. 2015. The patients were divided into the first-time calcium oxalate stone group (first-time group) and the recurrent of calcium oxalate stone group (recurrent group) according to the stone histories. The concentrations of clusterin in serum and urine, and the concentrations of serum interleukin (IL)-1β, IL-2 and IL-6 in the two groups were detected by ELISA. The independent risk factors influencing the recurrence of calcium oxalate kidney stones were analyzed by univariate and multivariate logistic regression analysis. Results Thirty-six patients were included in each group. Univariate analysis showed that there were no significant differences in age, gender, body mass index (BMI),estimated glomerular filtration rate (eGFR), maximum stone diameter or the concentrations of serum clusterin, IL-1β, IL-2 and IL-6 between the two groups (all P>0.05). The concentration of urinary clusterin in the recurrent group was significantly lower than that in the first-time group ([44.35±15.44] ng/mL vs[56.76±16.80] ng/mL, t=-3.262, P<0.05). Multivariate logistic regression analysis showed that urinary clusterin concentration (OR=0.939, 95% CI 0.900-0.979, P<0.05) was an independent risk factor influencing the recurrent of calcium oxalate kidney stone. Conclusion The concentration of urinary clusterin is decreased in patients with recurrence of calcium oxalate stone compared the first-time stone patients, suggesting that the clusterin in urine may be closely related to the recurrence of stones.