As one of the most lethal malignancies worldwide, hepatocellular carcinoma (HCC) has a high mortality rate, which is mainly due to the complex and multi‑step aberrations in gene expression associated with it. Small nucleolar RNAs (snoRNAs), non‑coding RNAs that are 60‑300 nucleotides in length, have been proposed to be closely associated with numerous human diseases, including HCC. However, the current knowledge regarding their clinical significance and mechanistic roles in HCC is limited. The present study comprehensively analyzed the snoRNA expression profiles in HCC and identified several ones that were dysregulated. The potential regulatory mechanisms of these snoRNAs were assessed via gene functional enrichment analyses. Univariate and multivariate Cox regression analyses were performed to identify snoRNAs that are independently associated with the risk of mortality. Subsequently, a prognostic index (PI) for survival prediction was established, which may serve as a prognostic biomarker for patients with HCC (hazard ratio, 3.023; 95% confidence interval: 1.785‑5.119; P<0.001). In addition, a series of bioinformatics analyses were performed to identify potential differences in the perturbation of pathways between high‑ and low‑risk groups. The PI developed in the present study was determined to have a moderate predictive value regarding the clinical outcome for HCC patients.