Objective To explore the effects of progressive nutritional support on soluble CD44 level and quality of life in patients with oral cancer. Method 65 patients diagnosed with oral cancer surgery at the Affiliated Oncology Hospital of Shandong First Medical University from December 2018 to December 2020 were randomly divided into a control group 32 cases and an experimental group 33 cases using a random number table method The control group received routine nutritional intervention while the observation group received progressive nutritional support. Patients in the control group received conventional nutritional intervention and patients in the observation group received progressive nutritional support. After continuous intervention for 7 days the levels of nutrition-related indicators body weight hemoglobin total protein prealbumin gastrointestinal symptoms abdominal pain abdominal distension diarrhea nausea vomiting and soluble CD44 standard CD44 CD44s and variant CD44 CD44v were compared between the two groups. After the intervention all patients were followed up for 4 weeks to compare the quality of life and its influencing factors. Result Compared with the control group the total protein 66. 72±3. 45 g / L vs 62. 45±3. 07 g / L and prealbumin 209. 41±23. 44 g / L vs 181. 41±20. 07 g / L levels in the observation group were significantly higher after 7 days of intervention P<0. 05 . The levels of CD44s 421. 75±32. 41 g / L vs 481. 43±30. 01 g / L and CD44v 60. 14±10. 12 g / L vs 67. 81±10. 01 g / L in the observation group were lower than those in the control group P< 0. 05 . Compared with the control group the incidence of abdominal pain abdominal distension diarrhea nausea and vomiting in the observation group was significantly lower 21. 2% vs 53. 1% P<0. 05 . The quality of life in the observation group was higher than that in the control group 83. 39±8. 44 vs 75. 69±6. 98 points P< 0. 05 . From the distribution of patients with different quality of life grades the difference between the observation group and the control group was statistically significant Z = - 2. 481 P < 0. 05 . Conclusion Progressive nutritional support can improve the nutritional status of patients reduce the level of soluble CD44 alleviate adverse reactions and improve the overall quality of life.