Purpose: Surgery has a negative effect on the mental, physical, and functional health of patients with oral cancer, which affects their quality of life (QOL). The study aimed to assess the effect of comprehensive nursing intervention on anxiety and QOL in postoperative patients with oral cancer. Methods: We investigated the level of anxiety and QOL of 200 postoperative oral cancer patients. After the comprehensive nursing intervention, the Beck Anxiety Inventory scale and European Organization for Research and Treatment of Cancer tools were used to assess the level of anxiety and QOL, respectively. Results: There was a statistically significant difference in terms of educational status (p=0.02), monthly income (p<0.01), cancer stage (p<0.01), and tumor metastasis (p=0.02). The experimental group experienced a significant decrease in anxiety (p=0.04), and their QOL was significantly higher (p=0.05) than that of the control group. Conclusion: Our study indicates that a comprehensive nursing intervention can lower the risk of surgical complications, enhance patients' psychological state by reducing anxiety, and enhance their QOL in patients with oral cancer.