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Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P=0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coef- ficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC. [ABSTRACT FROM AUTHOR]