Radiation-induced injury to the salivary glands is a recognized complication of radiotherapy for head and neck cancer. However, comprehensive diagnosis of salivary gland dysfunction remains challenging. Therefore, we conducted a retrospective study to assess the effectiveness of [68Ga]Ga-FAPI-04 PET/CT in diagnosing salivary gland radiation injury in patients with head and neck cancer.We initially established a reference range of SUV values for functionally normal salivary glands and developed criteria for definitively diagnosing salivary gland injury. Meanwhile, we retrospectively analyzed 63 patients who underwent [68Ga]Ga-FAPI-04 PET/CT after receiving radiotherapy for head and neck cancer. The SUVmax values of their parotid and submandibular glands were measured to assess the diagnostic value. Statistical analysis included binary logistic regression, receiver operating characteristic (ROC) curve analysis, and correlation analysis.Out of 63 enrolled patients, 50 (79.4%) were diagnosed with salivary gland injury after radiotherapy. [68Ga]Ga-FAPI-04 PET/CT yielded a lesion-level detection rate of 92.9% (91/98 lesions) and a negative predictive value of 88.1% (52/59 lesions). [68Ga]Ga-FAPI-04 PET/CT identified an optimal SUVmax cutoff value of 3.55(AUC, 0.87; 95% CI: 0.80, 0.94; P < 0.001) for diagnosing parotid gland injury, achieving 70.3% sensitivity and 96.8% specificity. For submandibular gland injury, the cutoff is 3.15(AUC, 0.74; 95% CI: 0.65, 0.84; P < 0.001), with a sensitivity of 88.6% and a specificity of 55.6%. The Bootstrap-adjusted ROC curves demonstrated 99.0% and 92.1% overlap with the original curves for parotid and submandibular glands. Meanwhile, the dual-threshold SUVmax approach-combined with submandibular attenuation or volume reduction-boosted specificity from 55.6 to 76.7% (+ attenuation) and 77.8% (+ volume reduction), improving performance by 21.1 and 22.2% points, respectively.The [68Ga]Ga-FAPI-04 PET/CT scan effectively indicates salivary gland injury in head and neck cancer patients undergoing radiotherapy. It may serve as a new method for comprehensive detection and diagnosis of salivary gland injury.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.