This study was to explore the curative effect of early enteral nutrition (EN) of three-cavity nasal jejunal tube (NJT) based on nano superparamagnetic iron oxide (SPIO) in treating severe acute pancreatitis (SAP). After the Fe3+ and Fe2+ were mixed, the ions were co-precipitated to generate Fe3O4 nanoparticles, which were used as seeds for the sodium citrate-auric acid reduction reaction to form the gold-coated SPIO nanoparticles. 90 patients with severe AP were selected and randomly rolled into blank group (group B), control group (group C), and experimental group (group E), with 30 cases in each group. The three groups of patients were treated with complete parenteral nutrition support, EN through three-cavity NJT, an EN through three-cavity NJT under the guidance of SPIO nanoparticles, respectively. The resulted showed that the Acute Physiology and Chronic Health Evaluation (APACHE II) score (11.6±1.62) of the group E was much lower in contrast to the group B (16.34±1.45) and the group C (15.8±1.33) (P < 0.05). The computed tomography severity index (CTSI) in group E (5.03±0.65) was greatly lower than that in the group B (6.01±0.39) and the group C (5.89±0.44) (P < 0.05). Compared to the group B (14.5±1.25), the time required for the blood amylase to return to normal in the group C and the group E (11.8±1.39, 7.3±1.4) was shorter visibly (P < 0.05). The Visual Analogue Scale (VAS) scores during and after the placement of NJT were the lowest (P < 0.05). In short, the nutritional support through three-cavity NJT for patients with SAP was safe and effective, and had a positive effect on preventing infection and improving body function; in addition, the application of SPIO nanoparticles could help relieve patients’ pain and reduce adverse events.