Background: Existing treatment options including gemcitabine-based therapy and 5FU-based chemotherapy have limited prognostic impact in advanced pancreatic cancer (APC): the median overall survival (mOS) was 6-11 months for 1^st line therapy and 4-9 months for 2^nd line therapy. Nimotuzumab (nimo), anti-EGFR monoclonal antibody, had been shown to be more effective against APC in two previous studies, PCS07 (a phase II study in Germany) and NOTABLE study (a phase III study in China). Although the NOTABLE study obtained an encouraging result in China, it focused on a narrow population, KRAS wild-type patients. This study aimed to explore the efficacy and safety of nimo in the real-world population with APC. Methods: In this retrospective observational study, patients with APC were treated with nimo and followed up in a real-world clinical setting. Demographic and clinical data of these patients were collected from electronic medical records of First Affiliated Hospital of Xi’an Jiaotong University from April 2018 to June 2022. The primary efficacy endpoint was overall survival. Results: A total of 104 patients (median age was 60.5 years, range 34-84) treated with nimo and chemotherapy were analyzed. Among them, 11 (10.6%) were in stage II (AJCC 8^th edition), 23 (22.1%) were in stage III, and 70(67.3%) were in stage IV. The treatment regimen included gemcitabine plus nab-paclitaxel (AG, 80.77%), gemcitabine plus S-1 (GS, 10.58%) and others. The dosage of nimo was 200-400mg weekly, of which above 50% of patients received nimo 400 mg weekly. About 66 (63.5%) patients received nimo as 1^st line therapy and 38 (36.5%) patients as 2^nd line therapy. Up to July 5, 2022, the median follow-up time was 8.12 months and the mOS was not reached. The 1-year and 2-year OS rate were 80.2% and 74.4%, respectively. Further subgroup analysis showed that the mOS was also not reached in 1^st line treatment of nimo (median follow-up time 8.77 months) as well as the 2^nd line treatment of nimo (median follow-up time 7.62 months), showing a potential survival benefit. No grade 3 or above toxicities were observed. Conclusions: AG regimen was the most common therapy in clinical practice in China. The real world study displayed the addition of nimo would prolong the survival for APC, with a good safety profile.