Heat shock protein (HSP) 20, a low-molecular-weight HSP, is constitutively expressed in various tissues, such as smooth muscle, skeletal muscle, and liver. However, the characteristics and function of HSP20 have not been precisely understood. In the present study, we investigated correlations of expression levels of HSP20 in hepatocellular carcinoma (HCC) tissues and the surrounding tissues with clinical and pathologic characteristics in 53 resected HCC specimens. Although HSP20 was detected in all 53 HCC tissues, the expression levels were reduced compared with those in the adjacent non-tumor tissues. The expression levels of HSP20 were inversely correlated with tumor stage by TNM classification (p<0.01), presence of microvascular invasion (p<0.05), and tumor size (p<0.05). Our findings strongly suggest that HSP20 may play a role against the progression of human HCC.