HDGF (heparin-binding growth factor) is a multifunctional protein with both extracellular and nuclear roles in cancer pathogenesis. As a secreted protein, HDGF exhibits mitogenic activity for fibroblasts 1 and promotes tumor angiogenesis 2. Intracellularly, HDGF functions as a transcriptional regulator and DNA damage response modulator 3. In cancer contexts, HDGF mRNA stability is post-transcriptionally regulated through multiple mechanisms: m5C methylation by NSUN2 in bladder and hepatocellular carcinoma 45, and m6A methylation by METTL3 in gastric cancer 2. These modifications are recognized by reader proteins (YBX1 for m5C; IGF2BP3 for m6A) that enhance HDGF mRNA stability. HDGF's clinical significance spans multiple malignancies. Elevated HDGF expression correlates with poor prognosis in gastric cancer, bladder cancer, colorectal cancer, and endometrial carcinoma 42637. In colorectal cancer, HDGF promotes drug resistance by facilitating homologous recombination DNA repair 3. In nasopharyngeal carcinoma, HDGF regulates autophagy and chemosensitivity through p62 signaling 8. These findings establish HDGF as a multifaceted oncogenic driver with therapeutic potential across cancer types.