Surgical resection for primary and secondary hepatic neoplasms provides the best chance of cure. Advanced surgical techniques such as portal vein embolisation, two-staged hepatectomy and associated liver partition and portal vein ligation for staged-hepatectomy (ALPPS) have facilitated hepatic resection in patients with previously unresectable, bi-lobar disease. These techniques are frequently employed to ensure favourable clinical outcomes and avoid potentially fatal post-operative complications such as small for size syndrome and post-hepatectomy liver failure. However, they rely on the innate ability of the liver to regenerate. As our knowledge of liver organogenesis, liver regeneration and hepatocarcinogenesis has expanded in recent decades it has come to light that liver regeneration may also drive tumour recurrence. Clinical studies in patients undergoing portal vein embolisation indicate that tumours may progress following the procedure in concordance with liver regeneration and hypertrophy, however overall survival in these patients has not been shown to be worse. In this article, we delve into the mechanisms underlying liver regeneration to better understand the complex ways in which this may affect tumour behaviour and ultimately inform clinical decisions.