Background: NSCLC patients with high-risk pathological factors such as micropapillary (MP), solid (S), spread through air spaces (STAS), and visceral pleural invasion (VPI) have shown poor prognosis in previous studies. Furmonertinib (AST2818) is a novel, promising oral third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has demonstrated efficacy in tumours harbouring sensitive EGFR mutations and T790M resistance mutation. Here, we investigated the efficacy and safety of furmonertinib as adjuvant therapy in postoperative EGFR-mutated NSCLC patients with high-risk pathological factors. Methods: Patients who underwent radical lung cancer surgery with both EGFR mutations and MP/S/STAS/VPI were enrolled and received furmonertinib 80mg daily. The adjuvant therapy time (6-36months) depended on patients’ pathologic stage and physical conditions. The disease-free survival (DFS), safety and tolerability were evaluated. Results: This study retrospectively analyzed 69 patients who were pathologically confirmed adenocarcinoma, EGFR mutation positive (exon 19 deletion/L858R/exon 20ins), stage IA2-IIIA NSCLC. All of them had at least one high-risk pathological factor. There were 44 (63.8%) patients with MP, 14 (20.3%) with S, 10 (14.5%) with STAS and 33 (47.8%) with VPI. All patients were followed at least 13 months, and 24 (34.8%) of them have been followed up for over 21 months, median follow-up time was 18.5 months. By the cut-off date of March 1, 2023, all patients were alive and with no radiographic recurrence, including 3 (4.3%) with exon 20ins. During therapy, 26 (37.7%) patients had treatment-related adverse events (TRAEs) of any grade. The most common TRAEs were rash (12/69, 17.4%), mouth ulcer (6/69, 8.7%), diarrhea (5/69, 7.2%) and transaminase elevation (4/69, 5.8%). Only 2 (2.9%) patients had TRAEs of grade 3 or higher and 1(1.4%) of the two discontinued therapy. Conclusions: This is the first study to demonstrate that furmonertinib has good efficacy and a tolerable safety profile as adjuvant therapy in EGFR-mutated NSCLC patients with high-risk pathological factors who underwent radical lung cancer surgery.