Whether tenofovir disoproxil fumarate (TDF) is superior to entecavir in reducing hepatocellular carcinoma (HCC) risk among treatment-naïve chronic hepatitis B (CHB) patients remains controversial. We aimed to clarify this controversy. Several databases, including PubMed and Embase, were retrieved through November 2020. Cohort studies comparing the effectiveness of TDF and entecavir in reducing HCC incidence among treatment-naïve CHB patients were included if they reported multivariable-adjusted or propensity-score-matched risk estimates. A random-effects model was used to pool hazard ratios (HRs). Thirteen cohort studies, involving 4097 HCC cases and 80202 CHB patients, were included. Multivariable-adjusted meta-analysis revealed no significant difference in HCC incidence between TDF and entecavir groups (HR 0.86, 95% confidence interval 0.72–1.04), which was consistent with propensity-score-matched meta-analysis (HR 0.83, 95% confidence interval 0.66–1.03). Subgroup analysis showed that the observed similarity of TDF to entecavir for HCC prevention persisted in studies with follow-up length of ≥4 years but not in those with follow-up length of <4 years (Pinteraction<0.01). In conclusion, TDF is similar to entecavir in reducing HCC incidence among treatment-naïve CHB patients. Heterogeneous results of included studies may result from their disparity in follow-up length. Our findings should be treated with caution and need to be further confirmed.