BACKGROUND: High protein diet (HDP) promotes improvement of lean body mass in elderly without cancer; but the impact of high protein intake on muscle strength and mortality in cancer patients remains to be elucidated. This study evaluates the association between HPD on handgrip strength (HGS) and survival in older adults outpatients with advanced gastrointestinal cancer. METHODS: Ninety-one patients with advanced gastrointestinal cancer (>65% tumor stage III-IV) undergoing radiotherapy, chemotherapy or surgery were enrolled. Upon first oncological visit, tumor stage was assessed by a physician. Then, a nutritionist or a dietitian measured the body mass index (BMI), HGS by means of a dynamometer, and dietary food intake by using 24h food recall. Patients were stratified in HPD (i.e, ≥1.5 g/kg/d) or low protein diet (LPD: <1.5 g/kg/d). Kaplan-Meier curve was used to assess the survival since the cancer diagnosis. RESULTS: HPD was reported by approximately 30% of patients. Protein intake was significantly higher in HPD vs LPD patients (2.2 ± 0.8 vs. 0.8 ± 0.4 g/kg/d, respectively; p < 0.0001). No significant association was found between HPD and HGS, even after adjustment for physical activity, alcohol intake, smoking, sex, age, tumor stage, oncologic treatment and BMI (OR: 0.97 [95%CI: 0.88-1.08], p = 0.64), or for energy intake kcal/kg/day, leucine g/d and lipids g/d (OR: 0.93 [95%CI: 0.85-1.03, p = 0.19]. In addition, HPD group showed higher overall survival than LPD group (HPD: 14.7 vs. LPD: 7.3 months, p = 0.04). CONCLUSION: HPD is not associated with better muscle function as measured by HGS, but with overall survival in older adults outpatients with advanced gastrointestinal cancer. HPD may represent a strategy to mitigate the cancer-induced mortality and should be further explored.