Background Intervention with a mobile Health (mHealth) app can improve the efficacy of early detection of oral cancer and the outcomes for patients taking oral anticancer medications. The quality of life of oral cancer patients is significantly reduced within three months after surgery; also, their needs for nursing care and health information increase, mainly due to side effects and associated psychological problems. Objective This study aimed to evaluate changes in the care needs and quality of life of patients with oral cancer after receiving the intervention of a newly developed mHealth app. Methods After surgery, oral cancer patients were divided into an experimental group (n=50) who received the mHealth app intervention and a control group (n=50) who received routine health care and instruction. After 3 months of intervention, survey questionnaires were used to assess the patients’ quality of life, nursing care needs, and acceptance of the mHealth app. Results The physiological care needs were significantly decreased in the experimental group compared with the control group (P<.05). Although the differences were not statistically significant, the psychological needs, communication needs, and care support needs all improved after the mHealth app intervention. The overall improvement in quality of life was higher in the experimental group than in the control group (–7.24 vs –4.36). In terms of intention to use, perceived usefulness, and perceived ease of use, the acceptability scores of the mHealth app were significantly increased after 3 months of intervention (P<.05). Conclusions Compared with routine health care and instruction, for patients after surgery, the education/information intervention using the mHealth app significantly reduced their nursing care needs, improved their quality of life, and increased their acceptance of using an mHealth app on a mobile device. These findings can provide a theoretical basis for future health care app design and improvement. This study suggests that an mHealth app should be incorporated into the routine care of oral cancer patients to provide medical information quickly and improve their self-management abilities, thereby reducing the patients’ need for physiological care and improving their quality of life. Trial Registration ClinicalTrials.gov NCT04049968; https://www.clinicaltrials.gov/ct2/show/NCT04049968