BACKGROUND: The minimal clinically important difference (MCID) for the Gastrointestinal Quality of Life Index (GIQLI) is unknown, which limits its application and interpretation. This study aimed to estimate MCIDs for the GIQLI scores of patients after they had undergone cholecystectomy. METHODS: This study had 267 participants. All the participants completed the GIQLI and four anchor items, namely, “How would you describe your overall symptoms, emotions, physical functions, and social functions since your last visit?” The response options were “much worse,” “somewhat worse,” “same,” “somewhat better” and “much better.” The MCID was defined according to those who responded with “somewhat better.” RESULTS: The mean age of the participants was 57.81 +/- 14.93 years, and 37.08% of the patients were women. The MCID group included 67, 78, 44, and 22 patients with MCIDs of 6.42, 6.86, 7.64 and 6.46 points respectively for scores on the symptoms, emotions, physical functions, and social functions subscales, respectively. The effect sizes of four anchors in the “somewhat better” group (0.38-0.49) exceeded those of the same group (0.25-0.38). CONCLUSIONS: This study showed that after patients had undergone cholecystectomy, the clinically significant mean changes in their scores on the GIQLI subscales for symptoms, emotions, physical functions, and social function were respectively 6.42, 6.86, 7.64, and 6.46 points. After patients have undergone cholecystectomy, the MCIDs for the GIQLI subscales can play an important role in interpretation of the scores, application of them in clinical practice, and verification of treatment effects.