Objective <p>To explore the impact of graded nursing interventions based on a quantitative risk assessment system on psychophysiological stress responses in patients undergoing resection for primary liver cancer.</p> Methods <p>A total of 80 patients who underwent liver cancer surgery in the hepatobiliary and pancreatic surgery department of a tertiary Grade A hospital between January 2023 and December 2023 were randomly divided into an observation group and a control group, with 40 patients in each, using a random number table method. The control group received routine nursing care, whereas the observation group received a graded nursing plan based on a quantitative assessment system.</p> Results <p>Before the intervention, there was no statistically significant difference in Psychological Stress Response Questionnaire (SRQ) scores between the two groups. Following the intervention, SRQ scores decreased in both groups, with significantly lower scores in the observation group than in the control group (<i>P</i> &lt; 0.001). Similarly, no statistically significant differences in the Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores were observed between the groups before the intervention. After the intervention, both groups showed lower HAMA and HAMD scores than pre-intervention levels, with the observation group exhibiting significantly lower scores than the control group (<i>P</i> &lt; 0.001).</p> Conclusion <p>Graded nursing interventions based on quantitative assessment can effectively reduce postoperative psychological stress and negative emotional responses in patients undergoing surgery for primary liver cancer, thereby promoting recovery.</p> Trial registration <p>ISRCTN81587743, Registration date: 25/04/2025.</p> Clinical trial number <p>ISRCTN81587743.</p>