Objective: To investigate the efficacy of different nutritional support regimens used during hyperthermic intraperitoneal chemoperfusion (HIPEC) for patients with advanced gastric cancer and malignant ascites. Methods: Forty eligible patients were randomly designated to parenteral nutrition group (PN group) and parenteral nutrition plus enteral nutrition group (PN+EN group), with 20 cases in each group. Patients in PN group underwent HIPEC with simultaneous PN support and those in PN+EN group underwent HIPEC with simultaneous PN+EN support. The alterations in nutritional and immunological parameters before and after treatment, incidence of adverse reactions, time to gastrointestinal function recovery, length of hospital stay and treatment-related costs between the two groups were compared. Results: The nutritional and immunological parameters showed no significant difference between the two groups before treatment (all P>0.05). In both groups, the nutritional and immunological parameters were decreased at 4 and 7 d after treatment compared with the values before treatment, some of which showed a recovery trend in 7 d. The alteration levels in each nutritional parameter showed no obvious difference between the two groups (all P>0.05), but the recovery levels in all immunological parameters at 7 d after treatment in PN+EN group were significantly better than those in PN group (all P<0.05). Further, the time to bowel function recovery and length of hospital stay were shortened, and the treatment-related cost was reduced in PN+EN group compared with PN group (all P<0.05). No statistical difference was observed in incidence of adverse reactions between the two groups (P>0.05). Conclusion: During HIPEC for patients with advanced gastric cancer and malignant ascites, the PN plus EN support can help improve the immune function and promote the gastrointestinal recovery of the patients, and save medical cost.