China is an area with highly endemic hepatitis B virus (HBV) infection, with an estimated 93 million HBV carriers, resulting in approximately 330,000 deaths annually.¹ The predominant HBV genotypes in China are genotype B and C. Currently, nucleos(t)ide analogs are used for anti-HBV treatment. However, prolonged antiviral therapy may lead to drug resistance, which is associated with mutations in the reverse transcriptase region of the HBV genome. Several studies have shown that drug-resistant mutations existed in treatment-naïve patients with chronic hepatitis B (CHB). However, the prevalence rates of natural drug-resistant mutations varied in different reports.^2,3 Furthermore, the prevalence and clinical profile of natural drug-resistant mutations in CHB patients are not quite clear. Thus, the purpose of this study was to investigate the prevalence and clinical feature of natural drug-resistant mutations among treatmentnaïve CHB patients in a tertiary hospital in Huzhou, eastern China.