Esophageal squamous cell carcinoma (ESCC) is a malignancy with poor prognosis, which is often diagnosed at a late stage. Effective treatment options are limited when patients fail standard systemic therapy. The application of PD-1 inhibitors have led to a paradigm shift in the treatment of ESCC, but its efficacy as monotherapy is limited. Previous studies have shown that the antitumor effects may be reinforced when a PD-1 inhibitor is combined with radiotherapy or GM-CSF. This study aimed to report a case of a patient about advanced unresectable ESCC negative expression of PD-L1, who experienced tumor progression after chemoradiotherapy and targeted therapy.A significant systemic effect was seen after PD-1 inhibitor combined with GM-CSF and stereotactic body radiotherapy (SBRT) for metastatic lesions, however, severe pneumonia occurred after the triple-combination therapy. This study also reviewed several reports about the efficacy and safety of combination therapy.