【Abstract】 Objective To investigate the expression relationship between forkhead transcription factors of the O class 1 (FoxO1) and microRNA-142-3p (miR-142-3p) in oral squamous cell carcinoma (OSCC) and their significance. Methods From May 2016 to June 2018, 72 samples of OSCC tissue taken during the operation were selected as the observation group, and 50 normal morphologically adjacent oral mucosa tissues were selected as the control group. The relationships between the expressions of FoxO1, miR-142-3p and the clinicopathological characteristics of OSCC, and the correlation between them were compared. The influencing factors of prognosis adverse events of OSCC patients were analyzed by COX regression model. Results The positive expression rate of FoxO1 and miR-142-3p in the observation group were lower than those in the control group (P＜0.05). Comparison between high differentiation, medium differentiation and low differentiation, the positive expression rate of FoxO1 and expression of miR-142-3p decreased in turn (P＜0.05). Compared with stage Ⅰ~ⅡI, the positive expression rate of FoxO1 and expression of miR-142-3p in stage Ⅲ~Ⅳ were lower (P＜0.05). Compared with non lymph node metastasis, the positive expression of FoxO1 and expression of miR-142-3p in lymph node metastasis were lower (P＜0.05). Spearman showed that the expressions of FoxO1 and miR-142-3p in the observation group were positively correlated (P＜0.05). Univariate analysis showed that gender, age, BMI and pathological grade were not related to the poor prognosis of OSCC (P＞0.05), and the clinical stage, lymph node metastasis, FoxO1 and miR-142-3p were all the influencing factors of the poor prognosis of OSCC (P＜0.05). Multivariate analysis showed that clinical stage, lymph node metastasis, FoxO1, miR-142-3p were all independent risk factors for adverse events in the prognosis of OSCC patients (P＜0.05). Conclusion FoxO1 and miR-142-3p are closely related to the occurrence, development and prognosis of OSCC, FoxO1 may be targeted by miR-142-3p, and provide clinical reference for disease assessment and treatment target.