The coexistence of aspergillosis and squamous cell carcinoma (SCC) in the maxillary sinus was very rare. To our knowledge, this is the second report of coexistent SCC and aspergillosis in the maxillary sinus. A 58-year-old man underwent surgery for unilateral maxillary sinus infection with oroantral fistula. In the surgical specimen, SCC and aspergillosis were co-detected with routine and immunohistochemical stainings. Moreover, human papillomavirus 18 (HPV-18) was detected by polymerase chain reaction in the sinus specimen. The patient was re-operated with subtotal maxillectomy and has been followed up for two years without any evidence of recurrence or metastasis. Although it is not understood how aspergillosis could induce carcinoma formation, the chronic inflammation caused by prolonged fungal infection might be carcinogenic. Moreover, HPV-16 and -18 were another causative pathogens of SCC in the head and neck region. We recommend careful examination, including preoperative cytology, in patients with maxillary sinus fungal infections because of the potential for cancer development.