Oral squamous cell carcinoma (OSCC) is a malignant tumor occurring in the oral cavity. However, the molecular mechanism of OSCC is not clear. Bioinformatics was used to screen and identify role of collagen type X1 alpha 1 (COL11A1) on OSCC. 200 patients with OSCC were recruited. Clinical and follow-up data were recorded and COL11A1 expression levels were tested. Pearson chi-square test and Spearman correlation coefficient were used to analyze relationship between prognosis and related parameters in patients with OSCC. Univariate and multivariate Logistic regression, univariate and multivariate Cox proportional risk regression were used for further analysis, survival curve was drawn. Through bioinformatics analysis, OSCC patients with higher expression of COL11A1 have poor overall survival compare with OSCC patients with lower expression of COL11A1 (hazard ratios [HR] = 1.32, P = .047). Pearson chi-square test showed that age (P = .011), tumor grade (P = .023), COL11A1 (P < .001) was significantly correlated with prognosis of OSCC. Univariate Logistic regression analysis showed age (odds ratio [OR] = 2.102, 95% confidence intervals [95%CI]: 1.180-3.746, P = .012), tumor grade (OR = 1.919, 95%CI: 1.093-3.372, P = .023) and COL11A1 (OR = 12.775, 95%CI: 6.509-25.071, P < .001). Multivariate Logistic regression analysis showed that COL11A1 (OR = 12.066, 95%CI: 6.042-24.096, P < .001) was significantly associated with prognosis of patients with OSCC. Univariate Cox regression analysis showed that age (HR = 1.592, 95%CI: 1.150-2.205, P = .005), tumor grade (HR = 1.460, 95%CI: 1.067-1.999, P = .018) and COL11A1 (HR = 1.848, 95%CI: 1.340-2.548, P < .001) were significantly correlated with survival time of OSCC patients. Multivariate Cox regression analysis showed that tumor grade (HR = 1.466, 95%CI: 1.064-2.020, P = .019) and COL11A1 (HR = 1.645, 95%CI: 1.164-2.325, P = .005) were significantly correlated with survival time of OSCC patients. COL11A1 is significantly correlated with occurrence of OSCC. When COL11A1 is highly expressed, prognosis of patients with OSCC is worse and the survival time is shorter.