Background: Neoadjuvant chemoradiation is associated with improved OS, DFS and pCR in patients (pts) with locoregional ESCC. Nevertheless, it is still needed to explore more tolerable preoperative regimen in ESCC. Anlotinib is a multi-targeted angiogenesis inhibitor and has been demonstrated effective and safe as second-line monotherapy in ESCC patients in China (NCT02649361). The combination therapy might be a possible strategy. The preliminary results of nab-paclitaxel and cisplatin combined with anlotinib as NAT for ESCC had been reported in 2022 ASCO (e16015) and 2022 ESMO (1252P). Here, we updated the results. Methods: ESCC pts with clinical stage II-III and radical resectable potential were recruited. The calculated sample size was 62 and eligible pts received anlotinib (12mg, po, d1~14, q3w), nab-paclitaxel (175mg/m², iv, q3w) and cisplatin (20mg/m², iv, d1~3, q3w) for 2 cycles as NAT before surgery. Four weeks later, pts underwent radical surgery after exclusion of contraindications. The primary endpoint was ORR assessed by investigator per RECIST 1.1, secondary endpoints included R0 resection rate, DFS, OS, DCR and safety. Results: From Apr 2021 to Sep 2022, 40 eligible pts were enrolled. Among them, 29 pts underwent surgery after 2 cycles of NAT, 6 pts chose other treatment options, and 5 pts are still receiving NAT. Pts who had received surgery (n=29) were included in this analysis. In best overall response assessment, ORR was 86.2% (95%CI: 68.3-96.1%) and DCR was 100.0% (95%CI: 88.1-100.0%). R0 resection was achieved in all 29 pts who underwent subsequent esophagectomy. Among them, 4 pts (13.8%) were confirmed to be pCR. At the data cut-off date (September 15, 2022), the median DFS was not yet available. Among the 40 enrolled cases, the safety profile revealed that the most common treatment-emergent adverse events (TEAEs) were gastrointestinal reactions (80.0%), liver damage (15.0%), nausea (12.5%), hypokalemia (10.0%) and myelosuppression (10.0%). Grade 3 TEAEs occurred in 2 pts (5.0%) included neutropenia (2.5%) and gastrointestinal reactions (2.5%). Conclusions: Anlotinib in combination with nab-paclitaxel and cisplatin is safe and feasible as neoadjuvant therapy in patients with ESCC.