In general, our results suggest a critical role of the PPIAP22/miR-197-3p/PPIA axis in the progression of HCC by increasing malignancy of tumor cells and regulating the immune cell infiltration, especially macrophage, through the CCL15-CCR1 or CXCL12-CXCR4/CXCR7 pathway. This evidence concerns the gene PPIAP22 and hepatocellular carcinoma.