Background: Mounting evidence have shown that fecal microbiome can act as biomarkers for diagnosing colorectal cancer (CRC). Recent studies demonstrate that oral microbiome is concordant with gut microbiome. The role of oral microbiome in colorectal cancer has not been fully illustrated. Methods: We collected preoperational saliva with a final cohort of 237 patients who underwent surgical resections or colorectal endoscopy in XX Hospital from January 2018 to January 2020. Clinical demographics, comorbidities and oral conditions were obtained from medical records or questionnaires. Salivary microbial biomarkers were detected by quantitative polymerase chain reaction (PCR) after DNA extraction. Multivariate logistics regression analysis was employed to analyze the risk factors for colorectal cancer. A four-variable prediction model was constructed based on the logistics analysis.Results: Among the 237 patients enrolled, there were 95 endoscopy confirmed healthy control and 142 pathologically confirmed colorectal adenocarcinoma patients. Logistics regression analysis demonstrated that the risk factors associated with CRC included age at diagnosis (OR=1.111, 95%CI=1.072-1.151), male sex (OR=2.111, 95%CI=1.068-4.175), oral hygiene index (OR=1.769, 95%CI=1.116-2.804) and relative salivary Desulfovibrio desulfuricans (Dd) abundance (OR=1.156, 95%CI=1.05-1.272), based on which a four-variable model was developed. The four-variable model had good discriminative (Brier score=0.144, Concordance index=0.866) and calibration (0.834) abilities after bias correction. Conclusions: Elevated salivary Dd level is an independent risk factor for CRC. We have developed a four-variable model that could help identify at-risk patients for CRC.