Background: Several studies were conducted to explore the clinicopathological characteristics and prognostic value of heat shock proteins in hepatocellular carcinoma (HCC). However, the results remain controversial. To address this gap, we conducted a systematic review and meta-analysis.Methods: The eligible literature was obtained from PubMed, Cochrane library, Web of science, Embase, Chinese National Knowledge Infrastructure and Wan Fang databases. We used the odds ratio (OR) and hazard ratio (HR) as the suitable parameters to assess the clinicopathological features and prognostic value of heat shock proteins (HSPs) in hepatocellular carcinoma (HCC) patients. The statistical analysis was performed using STATA 16.0 software.Results: After inclusion and exclusion of studies based on the eligibility criteria, a total of 1809 hepatocellular carcinoma patients from 19 studies were finally included. The results showed that heat shock proteins expression was not associated with overall survival (OS) of HCC patients (HR=1.34, 95%CI = 0.84-2.12, P = 0.216). In addition, the pooled analyses suggested that HSPs expression was significantly correlated with the unfavorable conditions for higher tumor differentiation (OR = 1.34, 95%CI = 1.08-1.66, P = 0.008), vascular invasion (OR = 1.29, 95%CI = 1.01-1.65, P = 0.039) and lymphatic metastasis (OR=1.63, 95%CI = 1.08-2.46, P = 0.021). Meanwhile, the pooled HR showed significant correlation between heat shock protein 27 (HSP27) expression and overall survival of HCC patients (HR=1.69, 95%CI = 1.24-2.31, P = 0.001).Conclusions: Our meta-analysis confirms that overexpression of HSPs may be directly involved in tumor differentiation and distant metastasis but cannot be considered as a biomarker for predicting the prognosis of HCC. However, the expression of HSP27 could be a potential prognostic predictor of HCC.