Aim To assess the clinical parameters and compare the stress and pain response between fast-track recovery protocol and conventional treatment in patients undergoing major liver resection. Methods Eighty-eight patients suffering from malignant liver tumours were surgically treated from May 2012 to March 2015. After randomisation, they were prospectively divided into two groups: group fast-track patients (n = 46) and group conventional treatment patients (n = 42). Demographic and clinical data were collected and patients were assessed with pain scale (behavioural observation scale and visual analog scale), while depression levels were evaluated with Zung self-rating depression scale and three Numeric Analog Scale self-reported questions. Peripheral blood samples were collected at time points: T1 on the admission day, T2 on the day of surgery and T3 on the day of discharge examining serum levels of adrenocorticotropic hormone and cortisol. Conclusion Fast-track recovery protocols seem to be associated with improvement in several clinical parameters, without compromising, biologic or emotional stress in patients undergoing major liver resection.