Maxillary sinus membrane perforation may result from surgical or pathological destruction over maxillary posterior area, which may further leads to oroantral communication. This article is going to present a case of a 54-year-old male. The panoramic radiography and cone-beam computed tomography revealed the apical lesion over right maxillary premolars with maxillary sinus membrane perforation. Nonsurgical root canal treatment did not resolve symptoms. Therefore, the endodontic microsurgery was performed. The endodontic microsurgery minimizes the damage to the surrounding tissue and improve the success rates. After one year follow-up, his clinical symptoms and apical lesions were significantly improved, and the maxillary sinusitis had subsided. The aim of this article is to present our case and to discuss the clinical management of apical periodontitis of maxillary premolars with maxillary sinus membrane perforation.