Objectives Previous studies suggested that protein has a protective effect on the formation of biliary stones. The aim of the current study is the comparison between the effect of animal protein and plant protein on the formation of biliary stone. One hundred and ten cases who had the history of biliary stone disease and 230 controls who were normal in terms of biliary diseases enrolled in this study. Food frequency questionnaire was used for the nutritional assessment; moreover, demographic and anthropometric data, in addition to habitual history and comorbidities were collected by a questionnaire. Results Plant protein consumption was significantly lower in cases compared to controls (p=0.03). Furthermore, the relationship between biliary stone disease and animal protein intake was significant in crude model for men (OR: 1.03, 95% CI=1.01-1.05) and both sex together (OR: 1.01, 95% CI=1.00-1.01). In addition, the risk of biliary stone was significantly lower in patients with higher consumption of plant protein (for women: OR: 0.94, 95% CI=0.89-0.99, for both sex: OR: 0.96, 95% CI=0.93-0.99). Plant proteins have a significant negative effect on the formation of biliary stone disease compared to animal proteins.