ObjectiveTo analyze the effects of alcohol consumption on oral flora of middle-aged and elderly men from the core area of southwestern China, and explore the relationship between excessive-alcohol-consumption-related flora and alcohol-related cancer.MethodsFrom March to June 2018, saliva samples of target subjects were collected for 16S ribosomal RNA gene sequencing, and a questionnaire survey which took drinking history of each participant as the target variable was conducted. According to the amount of alcohol consumed, the subjects were divided into non-drinking group, moderate-drinking group, and excessive-drinking group. The microbial analysis of α diversity, analysis of group difference of oral flora abundance, bacterial function prediction, and receiver operating characteristic (ROC) curve model prediction were carried out.ResultsA total of 59 subjects were included. There were 23 cases (39.0%) in the non-drinking group, 23 cases (39.0%) in the moderate-drinking group, and 13 cases (22.0%) in the excessive-drinking group. The average age was (61.90±8.85) years. Excessive drinking increased the abundance of oral flora (P<0.05), and could change the abundance of specific genus such as Peptostreptococcus and TM7［G-6］ (P<0.05) and regulate cancer-related pathways (P<0.05). ROC analysis found that a panel of three genus oral bacteria such as TM7［G-6］ might effectively distinguish the non-drinking group from the excessive-drinking group (area under curve=0.915).ConclusionsGenus of Peptostreptococcus and TM7_［G-6］ are the potential oral flora biomarkers for the excessive-drinking of target subjects. Some excessive drinking-related flora are closely related to oral cancer.