Background <p>Antiviral treatment reduces, but does not eliminate, the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Predicting HCC risk in this population remains challenging. This study aimed to use dynamic changes in liver stiffness measurement (LSM) obtained using two-dimensional (2D) shear-wave elastography (SWE) to predict HCC in patients with non-cirrhotic and cirrhotic CHB who had well-controlled viremia.</p> Methods <p>We retrospectively enrolled 303 patients with CHB (45 patients with cirrhosis) who had well-controlled viremia (hepatitis B virus DNA &lt; 100 IU/mL for ≥ 6 months) during antiviral treatment. Patients were followed up every 3–6 months and had two to twelve reliable LSMs using 2D SWE. Clinical and laboratory variables, single LSM, change between two LSMs, and dynamic LSM changes were analyzed using least absolute shrinkage and selection operator and multivariable Cox regression analysis to identify risk factors for HCC. Dynamic LSM changes were classified into sustained low LSM (all LSMs ≤ 8.1&#xa0;kPa), unstable LSM (LSM ≤ 8.1&#xa0;kPa at least once and &gt; 8.1&#xa0;kPa at least once), and sustained high LSM (all LSMs &gt; 8.1&#xa0;kPa).</p> Results <p>Among the 303 patients, 27 developed HCC. In the multivariable analysis, sustained high LSM in dynamic LSM changes (HR = 11.624, 95% CI: 4.241–31.861; <i>P</i> &lt; 0.001; compared with sustained low LSM) and older age (HR = 1.046, 95% CI: 1.009–1.084; <i>P</i> = 0.013) independently predicted HCC. A novel model combining age and dynamic LSM changes achieved a C-index of 0.845 for internal validation, demonstrating reliable agreement between the predicted and observed probabilities of HCC development. The novel model showed better performance in non-cirrhotic patients with a C-index of 0.860, whereas the C-index was only 0.634 in cirrhotic patients.</p> Conclusions <p>Dynamic LSM changes can predict HCC in patients with CHB who have well-controlled viremia, especially in non-cirrhotic patients.</p>