HNF4α, a transcription factor, plays a vital role in regulating functional genes and biological processes. Its alternative splicing leads to various transcript variants encoding different isoforms. The spotlight has shifted towards the extensive discussion on tumors interplayed withHNF4α abnormalities. Aberrant HNF4α expression has emerged as sentinel markers of epigenetic shifts, casting reverberations upon downstream target genes and intricate signaling pathways, most notably with cancer. This review provides a comprehensive overview of HNF4α's involvement in tumor progression and metastasis, elucidating its role and underlying mechanisms.