Hepatocellular carcinoma (HCC) development is ameliorated with nucleos(t)ide agent (NA) therapy for hepatitis B virus (HBV)-related cirrhosis patients. This study investigates whether liver stiffness (LS) measurement at complete virological response (CVR) was useful in predicting HCC development. Between July 2006 and August 2016, HBVrelated cirrhosis patients with potent NA (entecavir/tenofovir) with the first LS measurement during CVR and with serial LS were enrolled. Patients developing HCC 6 months after potent NA or before the first LS measurement were excluded. Three hundred and seventy-one patients were enrolled. The median follow-up was 5.6 and 3.8 years from potent NA treatment and the first LS measurement respectively. Twenty-seven patients developed HCC. The 1-, 3-, 5-and 7-year cumulated incidences of HCC occurrencewere 0%, 2.8%, 5.8% and 9%, respectively. In addition to age > 57 years, LS > =21.5 kPa (HR: 3.86, 95%CI: 1.67-8.94) was an independent factor associated with HCC occurrence in multivariate analysis. However, the magnitude of change in LS was not associated with HCC development. For the first LS in HCC prediction, the performance was 0.636. There were two to thirteen LS measurements during CVR. The change in LS was classified into four patterns stratified by the first and serial LS. Compared with those with serial LS < 21.5 kPa, patients with LS > =21.5 kPa tend to have higher HCC occurrence (P = .062). In summary, LS at CVR was an independent factor associated with HCC development for HBV-related cirrhosis patients with potent NA. However, LS was not satisfactory in the prediction performance of HCC development. K E Y W O R D S hepatic cirrhosis, hepatitis B virus, hepatocellular carcinoma, liver stiffness, nucleos(t)ide agent