Background <p>We conducted a Phase II study to assess the efficacy and toxicity of nab-paclitaxel (nab-PTX) and cisplatin in combination with concurrent radiotherapy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC).</p> Methods <p>Forty-two patients with locally advanced ESCC received nab-paclitaxel (75&#xa0;mg/m²) and cisplatin (25&#xa0;mg/m²) on days 1, 8, 15, 22, and 29 of radiotherapy, with total radiation doses ranging from 50 to 64&#xa0;Gy. The overall response rate (ORR) and disease control rate (DCR) were defined as primary endpoints, while progression-free survival (PFS), overall survival (OS), and treatment-related toxicity were considered secondary endpoints.</p> Results <p>Between February 2019 and April 2023, 42 patients who met the inclusion criteria participated in the study, 36 (85.7%) of whom were male, with a median age of 62.5 years (IQR: 57.0-66.3). All participants were classified as having clinical stage III or IV disease. Of the 42 patients, 28 (66.7%) completed all planned chemoradiotherapy sessions, whereas 35 (83.4%) completed at least four cycles of chemotherapy, with a median of five cycles (range: 1–5). In the efficacy assessment, the ORR was 73.8%, and the DCR was 90.5%. After a median follow-up of 28.1 months (IQR: 19.9–55.8), the 1-year PFS and 1-year OS rates were 57.1% and 88.0%, respectively. The most common grade 3 or 4 adverse event (AE) was leukopenia (38.1%), with no treatment-related deaths observed.</p> Conclusions <p>The combination of nab-paclitaxel and cisplatin, administered on a weekly schedule with concurrent radiotherapy, demonstrated promising antitumour activity and an acceptable safety profile in patients with ESCC.</p> Trial registration <p>The trial was registered at <a href="https://clinicaltrials.gov">https://clinicaltrials.gov</a> under the identifier ChiCTR1900021079 in January 2019.</p>