Controversy exists about whether antiviral therapy (AVT) should be recommended for compensated cirrhosis patients with chronic hepatitis B virus (HBV) infection and detectable, but low, serum HBV-DNA levels. A retrospective cohort of 385 treatment-naïve, HBV-related compensated cirrhosis patients (mean age: 51.1 ± 9.7 years; 66% male) with low HBV-DNA levels (<2,000 IU/mL) was assessed for the development of hepatocellular carcinoma (HCC). During a median of 5.6 years of follow-up, HCC had developed in 37 (9.6%) patients. The 5-year cumulative HCC incidence rate was 2.2%, 8.0%, and 14.0% for patients with undetectable HBV DNA (<12 IU/mL), low HBV-DNA levels plus normal alanine aminotransferase (ALT) levels, and low HBV-DNA levels plus elevated ALT levels at baseline (P = 0.011). During follow-up, 71 patients maintained undetectable HBV-DNA levels, and 126 experienced HBV-DNA elevation over 2,000 IU/mL. AVT was initiated in 77 patients. In patients without AVT, the 5-year cumulative HCC incidence rates were 13.3%, 8.8%, and 1.4% for those who experienced HBV-DNA elevation, those who maintained detectable, but low, HBV-DNA levels, and those who maintained undetectable HBV-DNA levels, respectively. The 5-year cumulative HCC incidence rate was 5.9% for patients who started AVT; longer AVT duration and longer complete virological response (<12 IU/mL) duration was associated with lower HCC risk.