Introduction The primary objective of this systematic review is to assess the effect of neoadjuvant chemotherapy on liver regeneration after liver resection (LR) or portal vein embolization (PVE) in patients with liver metastasis from colo-rectal cancer. The secondary objectives are to evaluate the impact of the type of chemotherapy, number of cycles and time between end of treatment and procedure (LR or PVE) and to investigate whether there is an association between degree of hypertrophy and

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... stoperative liver failure. Methods The design of this systematic review will follow the current recommendations of PRISMA. After an exhaustive literature search with pre-established criteria, two researchers will individually screen the identified records, according to a list of inclusion and exclusion criteria. Primary outcome will be future liver remnant regeneration rate. All data will be registered in a predesigned database. In the event of a substantial heterogeneity of selected articles, a narrative systematic review will be performed. Discussion The results of this systematic review may help to better identify the patients affected by liver metastasis that could present low regeneration rates after neoadjuvant chemotherapy. These patients are at risk to develop liver failure after extended hepatectomies and therefore are not good candidates for such aggressive procedures. Systematic Review Registration PROSPERO registration number: CRD42020178481 (July 5th 2020).