Objectives: The aim of this study was to compare the efficacy and safety of thermal ablation, focusing on radiofrequency ablation (RFA) and microwave ablation (MWA), for hepatocellular carcinoma (HCC) using US-, CT-, and MR-guidance. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for studies comparing US, CT, and MR guidance in thermal ablation for HCC. Observational studies and randomized controlled trials (RCTs) were included. Overall survival (OS), local tumor recurrence (LTR), primary technique effectiveness (PTE), and major complications were assessed with network meta-analysis. Results: One RCT and 13 retrospective cohort studies reporting on 2349 patients were included. For OS at 3 years, compared to CT, US had hazard ratios (HRs) of 0.98 (95%CI: 0.77–1.26), and MR had HRs of 1.60 (95%CI: 0.51–5.00); For OS at 5 years, US had HRs of 0.80 (95%CI: 0.64–1.01), and MR had HRs of 1.23 (95%CI: 0.52–2.95) compared to CT. LTR rates, PTE, and major complications did not show statistical significance among the three guidance modalities (LTR: RR = 0.29 (95%CI: 0.08–1.14), p = 0.97 MR vs. CT; RR = 0.25 (95%CI: 0.06–1.02), p = 0.97 MR vs. US; PTE: RR = 1.06 (95%CI: 0.96–1.17), p = 0.90 MR vs. CT; RR = 1.08 (95%CI: 0.98–1.20), p = 0.90 MR vs. US. Major complications: RR = 0.27 (95%CI: 0.13–0.59), p = 0.94 MR vs. CT; RR = 0.41 (95%CI: 0.10–1.74), p = 0.94 MR vs. US). Conclusions: CT-, US-, and MR-guided RFA and MWA are equally effective and safe for HCC patients.