Objective To investigate the clinical values of laparoscopic radiofrequency ablation in liver cancer and its impacts on serumal VEGF and MMP-2. Method From Jan, 2012 to Dec, 2013, a series of patients with primary liver cancer were studied, patients were randomly signed into LAFA group or control group. During the study period, LRFA group were treated with laparoscopic radiofrequency ablation combined with FOLFOX4 chemotherapy while patients in control group were treated with PIAF chemotherapy only. The primary outcomes were the Health related quality of life score (HRQL), the degree of solid tumors classification, progression-free survival duration and 2-year mortality. The secondly primary outcomes included the level of serumal VEGF and MMP-2. Result When compared with the control group, patients in LRFA group got a significantly lower rate of disease progression (28.33 % vs 50.00 %, P = 0.015); a longer progression-free survival duration (500 vs 380 d, P = 0.013); a higher HRQL (80.33 ± 5.84 vs 65.87 ± 9.59, P = 0.000); a significantly lower level of VEGF at 7 days, 14 days, 28 days and 6 months after the clinical intervention were started (all P values were 0.000); a significantly lower level of MMP-2 at 14 days, 28 days and 6 months after the clinical intervention were started (the P values were 0.003, 0.001 and 0.000). Conclusion Laparoscopic radiofrequency ablation improved the long-term clinical outcomes and decreased the serumal level of VEGF and MMP-2.