The recurrence of head and neck squamous cell carcinoma (HNSCC) after surgical resection continues to pose a major challenge to cancer treatment. Advanced HNSCC exhibits a low response rate to immune checkpoint blockade (ICB), while photothermal therapy (PTT) can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy. In this regard, we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose (OBC), thrombin (TB), and gold nanocages (AuNCs) containing anti-programmed death 1 (PD-1) antibody (αPD-1@AuNCs), which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence. The αPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared (NIR) irradiation, which activated a potent antitumor immune response. More importantly, the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells, when combined with local ICB therapy, which effectively avoided the tumor recurrence in a HNSCC postoperative mice model. Overall, the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.