Background Recently, microRNA-221 has been found to be abnormally expressed in hepatocellular carcinoma; however, its clinical value has not been summarised. This meta-analysis aimed to assess the prognostic significance of miR-221 in hepatocellular carcinoma. Material and Methods PubMed, Science Direct, Web of Science, Scopus, Ovid MEDLINE, EMbase, Google Scholar, the Cochrane Library, CNKI, CBM, VIP and Wanfang databases were searched for eligible articles. The endpoints included overall survival, progression-free survival, recurrence-free survival, metastasis-free survival, disease-free survival. Hazard ratios with 95% confidence intervals were used to explore the relationship between miR-221 expression and clinical survival results of liver cancer patients. Subgroup analysis and sensitivity analysis were performed. Begg's test and Egger's test were conducted to evaluate publication bias. Results A total of nine studies including 607 patients were recruited for this meta-analysis. The pooled hazard ratios displayed that high miR-221 expression was remarkably associated with poorer overall survival (hazard ratio = 1.91, 95% confidence interval: 1.53-2.38, p < 0.01) and unfavourable progression-free survival/recurrence-free survival/metastasis-free survival/disease-free survival (hazard ratio = 2.02, 95% confidence interval: 1.58-2.57, p < 0.01). The results of Begg's test and Egger's test did not exhibit obvious publication bias. Conclusions High expression of miR-221 can predict poor outcome of hepatocellular carcinoma. miR-221 can be used as a promising prognostic biomarker of hepatocellular carcinoma.