Among the total cancer deaths, esophageal cancer ranks sixth in mortality. Radiotherapy and chemotherapy remain the main treatments for unresectable, locally advanced esophageal cancer, but a relapse and drug resistance are still common. The optimized choice for therapeutic schemes with low toxicity and a high quality of life is unclear when local progression occurs after radiotherapy and chemotherapy. Fluoroscopy-guided photodynamic therapy (PDT) on patients with recurrent esophageal cancer in whom the endoscope cannot pass may be used as a salvage treatment, and nanoparticle albumin-bound paclitaxel (Nab-P) has been shown to be effective for advanced esophageal cancer. The combination of PDT and Nab-P might be an effective and tolerable option for advanced esophageal cancer. The authors present a 65-year-old male patient diagnosed with esophageal squamous cell carcinoma (ESCC) and confirmed to have developed local progression after receiving radiotherapy and chemotherapy. Severe esophageal stenosis, mild malnutrition and anemia, and radiation pneumonia were found when he was admitted to the authors’ hospital. For rapid reduction of tumor burden and to restore normal diet, he received PDT by the X-ray fluoroscopy positioning method and Nab-P chemotherapy. The patient obtained clinical benefit from these treatments, and his quality of life improved. This case demonstrates the potential advantages of fluoroscopy-guided PDT combined with Nab-P in reducing the tumor load, preserving organ function, and improving the quality of life, as well as the beneficial effect on locally advanced esophageal cancer after radiotherapy and chemotherapy. This combination therapy provides an alternative for the clinical treatment of locally advanced esophageal cancer and it has broad prospects in treatment of the disease. Herein, the authors report a case of a patient with ESCC who suffered locally progressive disease after chemotherapy and radiotherapy as well as malnutrition and mild anemia because of feeding difficulties. The patient was treated with PDT, which was assisted by a new positioning technique of X-ray fluoroscopy and Nab-P chemotherapy, and finally achieved clinical benefits. In addition, a modified transnasal feeding tube was also applied in the process of fluoroscopy-guided PDT in this article.