AbstractBackground & AimsProgresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver‐related events associated with the use of chemotherapy in these patients.MethodsForty‐nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD‐10 codes K70‐K74, and matched 1:2 to non‐cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver‐related events and survival rate were compared.ResultsPatients with cirrhosis (Child–Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child–Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver‐related versus 0% in matched controls. WHO‐PS stage > 1 (HR 3.74, CI95%: 2.13–6.57, p < .001), TNM‐stage M1 (HR 3.61, CI 95%: 1.82–7.16, p < .001), non‐colorectal cancer (HR 1.73, CI 95%: 1.05–2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39–3.70, p < .001) were independent prognostic factors of 2‐year mortality, whereas cirrhosis was not.ConclusionsChemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes.