Purpose <p>To identify the classes of sleep quality trajectories in patients with hepatocellular carcinoma (HCC) and analyze differences in patient characteristics across these classes and to explore the relationship between sleep quality trajectory and quality of life (QOL) in patients.</p> Methods <p>A total of 205 patients completed sleep quality assessments at four time points (before surgery and 1, 3, and 6&#xa0;months after surgery). Classes of heterogeneous sleep quality trajectories were identified using a latent class mixed-effects model. The differences in the characteristics of patients across classes were identified by unordered multicategorical logistic regression. The relationship between sleep quality trajectory and QOL was assessed using a generalized estimation equation model.</p> Results <p>Three latent classes of sleep quality trajectories were identified in HCC patients: persistent good sleep (19.5%); persistent poor sleep (75.6%); and worsening (4.9%). Depression, fatigue, comorbidities, and drinking were associated with an increased odds of belonging to the persistent poor sleep class compared to the persistent good sleep class. Tumor size ≥ 5&#xa0;cm and comorbidities were associated with an increased odds of belonging to the worsening class. The decreases in QOL from admission to 1, 3, and 6&#xa0;months after surgery were significantly higher for patients in the worsening class compared to patients in the persistent good sleep class (all <i>P</i> &lt; 0.001).</p> Conclusion <p>The sleep quality trajectories in patients with HCC were characterized by three latent classes; patients in these classes differed in disease characteristics, psychological, and physical symptoms. Sleep quality worsening can lead to significant declines in the QOL of patients after surgery.</p>