The risk of renal events in HBsAg-positive cancer patients receiving tenofovir disoproxil fumarate (TDF) or entecavir (ETV) antiviral prophylaxis during chemotherapy has not been evaluated. This study aimed to evaluate the renal safety of TDF and ETV during chemotherapy. Consecutive, 219 HBsAg-positive cancer patients treated with TDF (n=106) or ETV (n=113) for antiviral prophylaxis during chemotherapy with baseline serum creatinine (SCr) <1.2mg/dL were retrospectively enrolled. Serial SCr levels and estimated glomerular filtration rate (eGFR) were monitored. The incidence of acute kidney injury (AKI) during antiviral prophylaxis was 33% and 38.9% in TDF and ETV groups, respectively (P=0.441), while the incidence of sustained kidney injury was 11.3% and 11.5%, respectively (P=1.000). By multivariate analysis, diuretics use (hazard ratio (HR)=2.011, P=0.042) and serum albumin levels (HR=0.441, P=0.001) were independent predictors of AKI; serum albumin levels (HR=0.252, P=0.002) was the only factor associated with sustained kidney injury; age (HR=2.752, P<0.001), baseline SCr levels (HR=3.386, P<0.001), and serum albumin levels (HR=0.437, P=0.001) were factors associated with a new eGFR <60mL/min. 34.9% of patients in TDF group and 35.4% in ETV group had deteriorated chronic kidney disease (CKD) stage at the end of follow-up, respectively. There were no significant differences in the risk of renal events or CKD stage migration between TDF and ETV groups. Renal events may develop in about one-third of HBsAg-positive cancer patients undergoing chemotherapy. The risk of renal function impairment was comparable between patients treated with TDF and ETV antiviral prophylaxis.