Objective. To explore the effects of different repair and reconstruction methods combined with psychological intervention on the quality of life and negative emotion of patients with oral cancer. Methods. 180 patients with oral cancer treated in our hospital from January 2018 to January 2020 were randomly divided into group A, group B, and group C, with 60 cases in each group. Group A and group B were repaired with submental island flap and free flap, respectively. Group C was divided into two groups, and group C was treated with routine nursing intervention. Group A and group B received psychological intervention. Clinical symptom scores, complication rate (CR), quality of life (according to the University of Washington quality of life questionnaire, UW-QOL), and negative emotion scores were compared. Results. After intervention, the clinical symptom scores and negative emotion scores of groups A and B were lower than those of group C (
P
<
0.001
), as well as the CR (
P
<
0.05
), and the UW-QOL scores of groups A and B were higher than those of group C (
P
<
0.05
), but no significant differences in these aspects were presented between group A and group B (
P
>
0.05
). The main factors affecting quality of life were swallowing/chewing, language, and saliva in group A; swallowing/chewing, language, and taste in group B; and appearance, swallowing/chewing, emotion, and language in group C. Conclusion. Psychological intervention can improve the mental state of patients with oral cancer after operation, optimize the effect of operation, and improve the quality of life. As the effect of psychological intervention on patients undergoing different repair and reconstruction methods is similar, it should be given according to patients’ actual condition in the clinic.