Objective The objective of this study was to explore the short-term effects and postoperative complications of ultrasound-guided percutaneous ethanol-lipiodol injection (PEI) combined with high-intensity focused ultrasound (HIFU) for the treatment of small hepatocellular carcinoma in a special or high-risk location. Methods Forty patients with small liver cancer in a special or high-risk location were randomly divided into two groups: 20 patients were treated with PEI combined with HIFU (P + H group), and 20 patients were treated with HIFU alone (H group). There were no significant differences in average age, liver function, tumor location, tumor number, or tumor size between the two groups (P > 0.05). Results Significant differences were observed in ablation parameters between the two groups (P < 0.05). Under the same power, ablation rates of the P + H group were significantly higher than those in the H group, and postoperative complications in the P + H group were significantly lower than those in the H group (P < 0.05). Conclusion The combination of PEI and HIFU has better clinical value than HIFU alone for small-cell liver cancer in special or high-risk locations.