Objective To analyze the high-risk factors of renal injury induced by tenofovir in population with chronic hepatitis B (CHB), so as to guide the rational use of tenofovir in clinical practice. Methods A total of 1 278 CHB patients who took tenofovir disoproxil fumarate (TDF) tablets in Anting Branch of The Third Affiliated Hospital of Naval Medical University (Second Military Medical University) from May 23, 2017 to Sep. 30, 2020 were selected by the Rbase rational usage of drugs intranet system. According to the inclusion and exclusion criteria, a total of 197 CHB patients were enrolled, including 143 in control group and 54 in renal injury group. The age, gender, comorbidities (hypertension and diabetes), baseline estimated glomerular filtration rate (eGFR) and body mass index (BMI) of patients between the 2 groups were compared. Univariate and multivariate logistic regression models were used to analyze the high-risk factors of renal injury in CHB patients caused by TDF. Results The average age and the proportion of hypertension in the renal injury group were higher than those in the control group, and the baseline eGFR was lower than that in the control group (all P<0.01). Univariate logistic analysis showed that age, hypertension, and baseline eGFR were related to renal injury indued by TDF (all P<0.01). Multivariate logistic analysis showed that older age (odds ratio[OR]=1.98, P=0.002), hypertension (OR=3.94, P=0.001) and lower baseline eGFR (OR=0.93, P<0.001) were independent risk factors for renal injury induced by TDF. After taking TDF, the risk of renal injury in CHB patients aged ≥ 60 years was 5.62 times of that in CHB patients aged <40 years (OR=5.62, P=0.001). Conclusion Renal function impairment is one of the common adverse reactions of TDF. CHB patients aged ≥ 60 years, with hypertension and low baseline eGFR are more likely to suffer from renal injury after taking TDF.