C-reactive protein (CRP) is an index of systemic inflammation. However, CRP is not usually assessed preoperatively. Hence the study intended to evaluate the preoperative serum CRP levels in oral squamous cell carcinoma (OSCC) patients and to analyse its relationship with the clinicopathologic characteristics. CRP values for 60 OSCCs and 30 healthy controls were evaluated using a CRP assessment kit and spectrophotometer. The Mann-Whitney U test, χ2 test, receiver operating characteristic (ROC) curve analysis, and logistic regression were applied. The CRP ranged from 0.3 to 86mg/L in OSCCs. CRP was significantly higher in OSCCs than in controls. A raised CRP was seen in 70% of OSCCs. CRP in OSCCs was associated with clinical nodal status and lymph node metastasis (LNM) (P<0.05). CRP was significantly higher in the metastatic than in the non-metastatic group. The area under the ROC was 0.819. The best cut-off value for predicting LNM was 8.65mg/L for the CRP with 0.767 sensitivity and 0.767 specificity (P<0.05). The cut-off revealed a significant association with LNM. Raised CRP may predict LNM. The CRP levels regressed significantly in relation to LNM. CRP could offer prognostic information beyond staging and histology. Hence, CRP can be added as an extension to known clinicopathologic parameters to predict the prognosis in OSCCs.