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Objectives: Acute kidney injury (AKI) is a recently observed side effect in patients after microwave ablation (MWA) of hepatocellular carcinoma (HCC) and is associated with negative outcomes. The aim of this study is to explore the risk factors of affecting the occurrence of AKI (stages 1b, 2, and 3), because they have a higher mortality rate than patients with AKI (stage 1a) and without AKI. Materials and methods: In this retrospective study, a total of 1,214 patients with HCC who were treated with MWA under ultrasound (US) guidance in our department between January 2005 and November 2017 were enrolled. We evaluated the influence of 20 risk factors. Univariate and multivariate analysis were used for statistical analysis. The possible risk factors of AKI after MWA for HCC were summarized. Results: AKI, AKI (stage 1a), and AKI (stages 1b, 2, and 3) after MWA were found in 34, 15, and 19 patients (2.80, 1.24, and 1.57%), respectively. Among 34 patients with AKI, 10 cases with AKI (stage 1a) and 6 cases with AKI (stages 1b, 2, and 3) recovered before their discharge without any treatment for AKI and 9 cases with AKI (stages 1b, 2, and 3) with further treatment. Four cases who had chronic renal failure before MWA of liver accepted renal dialysis. By univariate analysis, the number of antenna insertions (P = 0.027, OR = 3.3), MWA time ≥20 min (P = 0.029, OR = 4.3), creatinine (Cr)-pre above the upper limit of the reference value (P < 0.001, OR = 35.5), albumin (Alb)-pre (P = 0.030, OR = 0.9), and red blood cell (RBC)-pre (P < 0.001, OR = 0.3) were significant risk factors. By multivariate analysis, Cr-pre ≥ 110 μmol/L (P < 0.001, OR = 31.4) and MWA time ≥20 min (P = 0.043 OR = 9.9) were the independent risk factors. Conclusion: AKI (stages 1b, 2, and 3) is a relatively serious complication after MWA for HCC, which is related to MWA time and Cr-pre. It requires attention by clinicians. So it is of great necessity to assess the Cr-pre level and reduce the MWA time to <20 min to minimize the risk of AKI after MWA for HCC. [ABSTRACT FROM AUTHOR]