The number of cases with hepatocellular carcinoma (HCC) are on the increase. The aim of the present study was to investigate the clinical effect and relevant mechanism of combined sorafenib and radiofrequency ablation (RFA) in the treatment of the early small HCC. A total of 120 cases of patients with small HCC that presented during the period of May 2007 to June 2010 were selected and divided into the surgery (n=60) and RF (n=60) groups according to the treatment method employed. The surgery group was treated with a laparotomy resection and the RF group was treated with combined sorafenib and RFA, and a comparative analysis was made between the two groups with regard to recurrence rates, adverse reactions, and survival rates. After treatment of 1 month, the radical effective rate of the surgery and RF groups was 100%. Contrast-enhanced ultrasound images of the patients in the RF group were taken. During the 5-year follow-up, the tumor recurrence rate in the surgery group was 18.3%, significantly lower than that in the RF group where the tumor recurrence rate was 38.3% (P<0.05). The occurrence rate of postoperative pain, fever, abdominal bleeding, infection, and other complications of patients in the surgery group was significantly higher than the complication occurrence rate (P<0.05) of the patients in the RF group. The average survival time of the patients in the surgery group was 51.2±1.5 months and the survival rates during the first, third and fifth year were 90.7, 71.5 and 56.7%, respectively. Additionally, the average survival time of the patients in the RF group was 64.6±2.4 months and the survival rates during the first, third and fifth year were 91.1, 72.8 and 57.5%, respectively. The difference between the two groups was not statistically significant. The tumor-free survival rates in the surgery group during the first, third and fifth year were 87.8, 44.3 and 33.2%, respectively, while the tumor-free survival rates in the RF group during the first, third and fifth year were 86.2, 48.3 and 34.6%, respectively, and the difference between the two groups was not statistically significant. In conclusion, the combined sorafenib and RFA method, and laparotomy resection method have their advantages in the treatment of early small HCC, and under specific medical conditions, the former can partially replace the latter and be used as a preferred treatment means in the treatment of early small HCC.