Objective To explore the impact of the intervention model based on self-efficacy theory on fear of progression (FoP), negative emotions, and cancer-related fatigue in patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization (TACE). Methods The clinical data of 94 patients with primary liver cancer were retrospectively analyzed. The patients were divided into control group and observation group according to different intervention methods, with 47 patients in each group. The control group received routine nursing mode after discharge, while the observation group received intervention model based on self-efficacy theory. Both groups were intervened for 3 months after discharge. The self-efficacy[General Self-Efficacy Scale (GSES)]at discharge and one- and three-month after discharge, FoP[Fear of Progression Questionnaire-Short Form (FoP-Q-SF)], negative emotions[Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS)], cancer-related fatigue[Revised Piper Fatigue Scale (R-PFS)], and quality of life[Quality of Life Questionnaire for Liver Cancer Patients (QOL-LC V2.0)] at discharge and three-month after discharge were compared between the two groups. Results One month and three months after discharge, the GSES scores of both groups gradually increased compared to those at discharge, and the scores of the observation group were higher than those of the control group (P < 0.05). Three months after discharge, the total and sub-dimension scores of FoP-Q-SF, SAS scores, SDS scores, and R-PFS were lower in both groups compared to those at discharge, and the observation group had lower scores than the control group (P < 0.05). Three months after discharge, the total and sub-dimension scores of QOL-LC V2.0 were higher in both groups compared to those at discharge, and the observation group had higher scores than the control group (P < 0.05). Conclusion The intervention model based on self-efficacy theory can enhance the self-efficacy of patients with primary liver cancer after TACE, relieve negative emotions and severity of FoP, improve cancer-related fatigue, and enhance the quality of life.