Objective: To determine the efficacy of sequential dual-target intensity-modulated radiation therapy combined with interventional therapy for giant liver cancer. Methods: Eighty-one eligible patients with giant liver cancer from January 2008 to January 2015 were enrolled. They were randomly divided into observational group and control group, and patients observational group (40 cases) underwent two-session interventional therapy followed by sequential dual-target intensity-modulated radiation therapy (30-40 Gy/15-20 F), and those in control group (41 cases) had a two-session interventional therapy followed by alternating hyperfractionated intensity-modulated radiation therapy (30-40 Gy/15-20 F). The efficacy and adverse reactions between the two groups were compared. Results: The AFP levels in both group were significantly decreased compared with their preoperative levels, and in observational group and control group, the overall response rate was 86.8% and 79.5%; the median survival time was 10.3 and 9.7 months, and the overall 6-month, and 1-, 2- and 3-year survival rate was 63.2% and 59.0%, 50.0% and 48.7%, 21.1% and 17.9%, 5.3% and 2.6%, respectively. The differences in all the above parameters between the two groups showed no statistical significance (all P>0.05). The incidence of grade 1/2 bone marrow suppression in observational group was lower than that in the control group (P<0.05) and the difference was statistically significant (P<0.05), but no significant difference was noted in incidence of other adverse reactions between the two groups (P>0.05). Conclusion: Either sequential dual-target intensity-modulated radiation therapy or alternating hyperfractionated intensity-modulated radiation therapy combined with interventional therapy can offer better clinical efficacy for giant liver cancer, with tolerable adverse reactions, so both methods are effective treatment modalities for giant liver cancer.