In this review, we provide important clues for understanding the key roles of the H19 functional network in signaling pathways and identifying new therapeutic targets for several cancers (Figure 1), such as gastric cancer, hepatocellular carcinoma (HCC), pancreatic cancer, colorectal cancer (CRC), breast cancer, thyroid cancer, non-small cell lung cancer (NSCLC), melanoma, Hodgkin’s lymphoma, choriocarcinoma, glioma, bladder cancer, osteosarcoma, multiple myeloma (MM), and oral and cholangiocarcinoma. The gene discussed is H19; the disease is hepatocellular carcinoma.