Objective To investigate the effect of febuxostat on renal protection compared to allopurinol in chronic kidney disease(CKD)patients complicated with hyperuricemia(HUA). Methods Seventy-eight CKD Ⅲ stage patients complicated with HUA were consecutively recruited in this study, and were randomized to febuxostat treatment group and allopurinol treatment group as 1:1 ratio for 6-month treatment. Change of estimated glomerular filtration rate(eGFR), serum creatinine(Scr), serum uric acid(SUA)and 24-hour proteinuria from baseline [Month 0(M0)] to Month 6(M6), and proportion of patients showing a >10% decline in eGFR from M0 to M6 were evaluated. Results The increase of eGFR from M0 to M6 was higher in febuxostat group compared to allopurinol group(P=0.012)and the proportion of patients showing a >10% decline in eGFR was lower in febuxostat group than that in allopurinol group(P=0.037). Further subgroup analysis revealed that the increase of eGFR from M0 to M6 was only elevated in febuxostat group compared to allopurinol group in CKD Ⅲb patients(P=0.023)but not in CKD Ⅲa patients(P=0.266). Besides, febuxostat slowed the increase of Scr(P=0.027)and reduced the level of SUA(P=0.019)from M0 to M6 compared to allopurinol, while no difference in the change of 24-hour proteinuria from M0 to M6 was found between two groups(P=0.131). No cardiovascular events occurred in either group for the entire observational duration. In addition, no difference was observed in adverse events between two groups(P=0.131), while rash occurrence rate was numerically lower in febuxostat group than in allopurinol group, but without statistical significance(P=0.076). Conclusions Febuxostat may delay the decline of eGFR, suppress the increase of Scr compared with allopurinol, therefore febuxostat presents a better renal protection in Stage Ⅲ CKD patients with HUA.