Appropriate sedation and analgesia are crucial for successful endoscopic procedures, patient safety, and satisfaction. Endoscopic resection for upper gastrointestinal tumors requires a deep sedation level because the procedure is lengthy and induces moderate to severe pain. Continuous patient consciousness assessment and vigilant vital signs monitoring are required for deep sedation. General anesthesia may unintentionally occur even during deep sedation for endoscopic tumor resection, which may cause unexpected complications, especially in high-risk patients. Previous studies have revealed that general anesthesia increases the en bloc resection rate and decreases the procedure time. Complications, such as perforation, aspiration pneumonia, and cardiopulmonary instability, including hypoxemia, hypotension, and arrhythmia, occurred more frequently in patients with sedation compared to those with general anesthesia. Therefore, general anesthesia demonstrated potential benefits in endoscopic treatment results and patient safety. General anesthesia should be considered a useful alternative for sedation in patients undergoing endoscopic gastrointestinal tumor resection. However, more high-quality prospective studies are required to determine the safety and effectiveness of general anesthesia in endoscopic upper gastrointestinal tumor resection because most studies comparing general anesthesia and sedation in these procedures have been retrospectively conducted and the results were inconsistent.