Researches indicated using low-frequency electromagnetic fields(EMF)induce tumor cellsapoptosis, inhibit angiogenesis, impeded proliferation of neoplastic cells. Since angiogenesis could be target for tumor therapy and regards to the fact that matrix-metalloproteinase(MMP) has great effect on angiogenesis process as an extracellular protease. The aim of this research, was investigating the synergic effects of saffron and EMF on MMP gene expression in MCF-7 cell line. Saffron extracted using freeze dryer. MCF-7 cells were grown in RPMI-1640 medium supplemented with %10FBS and incubated at37°C with%5CO2. After 24h cells were treated by saffron at concentration of 100,200,400and800μg/ml. 48h after treatment all flasks exposed with electromagnetic field (50Hz,0.04T) then total RNA was extracted and cDNA was synthetized using specific primer. Synthetized products were analyzed by Real Time PCR to determine expression level of MMP. Data analysis revealed inhibitory effect of saffron at concentration of 100,200,400and 800μg/ml on MMP gene expression in compare with control group with 5%,18%,15%and11% respectively (P˂0.05). Low-frequency electromagnetic field itself also could reduce MMP up to 8% in compare with control group which is remarkable at P˂0.05. Synergic use of saffron and electromagnetic field had inhibitory effect on gene expressionwith23%,20%,19%and16%respectively (P˂0.05). Results indicated decrease in the expression of MMP in the treated samples with both saffron and exposure by low frequency electromagnetic field compared to controls.