OBJECTIVE: The effect of probiotics on cognitive function and the risk of falling in cirrhosis patients have not been previously evaluated. We perform this protocol for systematic review and meta-analysis to evaluate the effect of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis. METHODS: An all-round retrieval will be performed in 5 electronic journal databases from their inception to March 2021, which comprise Medline, Pubmed, Embase, ScienceDirect, and the Cochrane Library by 2 independent reviewers. Data extraction was performed independently, and any conflict was resolved before final analysis. Only randomized clinical trials were included in this study. The main endpoints were cognitive function and risk of falls, and the secondary endpoints were fall incidence, health-related quality of life (HRQOL), systemic inflammatory response, gut barrier, bacterial translocation, and fecal microbiota. The risk of bias assessment of the included studies was performed by 2 authors independently using the tool recommended in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: We hypothesized that the multistrain probiotic improved cognitive function, risk of falls, and inflammatory response in patients with cirrhosis and cognitive dysfunction. CONCLUSION: This study expects to provide credible and scientific clinical evidence for the efficacy and safety of a multistrain probiotic on cognitive function and the risk of falls in patients with cirrhosis. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JKMTP.