Background: It is important to predict prognosis and risk of adverse events in patients with advanced gastric cancer receiving chemotherapy. Albumin-bilirubin (ALBI) grade is recently used as liver function assessment and prognosticator in hepatocellular carcinoma. Irinotecan is metabolized in the liver, so ALBI score may be useful for predicting irinotecan efficacy and safety. Methods: We conducted a retrospective multicenter study and investigated association between efficacy and ALBI grade in patients who received irinotecan monotherapy between January 2010 and December 2017. All patients had to receive fluoropyrimidine and platinum as prior therapy. The ALBI score is calculated by the equation: ALBI score = (log₁₀ bilirubin [µmol/L] × 0.66) + (albumin [g/L] ×−0.0852). As a result, ALBI grades 1, 2, and 3 were developed as follows: ALBI score ≤−2.60 (ALBI grade 1), >−2.60 to ≤−1.39 (ALBI grade 2), and >−1.39 (ALBI grade 3). Results: The number of patients with ALBI grade 1/2/3 is 100/68/5. In ALBI 1/2-3 patients, performance status 0/1/≥2 was 37/57/6 and 17/43/14, treatment line 2^nd/3^rd or later was 58/42 and 21/53, HER2 positive/negative 14/86 and 16/58, respectively. In ALBI 1/2-3 patients, median PFS was 3.3 and 2.3 months (HR = 0.684, P = 0.018) and median OS was 11.7 and 6.7 months (HR = 0.492, P < 0.001), respectively. In ALBI 1/2-3 patients, median treatment cycle which was 6 and 4 (P = 0.09) and RDI were significantly different was, and RDI was 0.80 vs 0.70(P = 0.027), respectively.Hematological AEs were observed in 88% and 87% (P = 1.000), severe hematological AEs (≥G3) were 41% and 58%(P = 0.040). Non-hematological AEs were 87% and 86%(P = 1.000), severe non-hematological AEs (≥G3) were 11% and 18% (P = 0.257), respectively. Severe AEs in more than 5% patients were leukopenia (12% and 18%), neutropenia (23% and 28%), anemia (16% and 31%), and anorexia (2% and 10%).In multivariate analysis, ALBI grade was associated with shorter OS (ALBI 1 and 2-3: HR 1.773 95%C.I. 1.184-2.654, p = 0.005). Conclusions: ALBI grade might be both prognostic factor and risk factor in treatment with irinotecan monotherapy for patients with AGC.