Objective: To investigate the ablative effect and safety of trans-catheter arterial chemoembolisation (TACE) combined with radiofrequency ablation (RFA), and TACE alone for the treatment of hepatocellular carcinoma and compare the changes in the level of relevant serum inflammatory and tumor markers. Study Design: Descriptive comparative study. Place and Duration of Study: Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, from January 2016 to June 2018. Methodology: Patients with hepatocellular carcinoma were randomly chosen and classified into combination group and TACE group, according to the treatment method. The 106 patients in the combination group were given RFA combined with TACE for treatment. The 112 patients in TACE group were given only TACE treatment. The objective response rate (ORR) and disease control rate (DCR) of short-term ablative effect, and adverse effect, serum inflammatory, and tumor markers' levels were compared for both groups before and one month after treatment. Results: ORR and DCR of combination group were significantly higher than those of TACE group: 84 vs. 58%, and 99 vs. 80%, respectively (p=0.013). The differences in the frequency of adverse effects were statistically significant (p<0.05). After treatment, vascular endothelial growth factor (VEGF), alpha fetoprotein (AFP), and matrix metalloproteinase (MMP) of both groups declined significantly (p<0.05), that of the combination group significantly lower than those of TACE group (p<0.05). After treatment, tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and hypersensitivity C reactive protein (hsCRP) of both groups declined significantly (p<0.05), that of combination group significantly lower than those of TACE group (p<0.05). Conclusion: TACE combined with RFA has better ablative effect than pure TACE in the treatment of hepatocellular carcinoma. It can effectively reduce the level of tumor active factor and improve microinflammed state of the body.