Lung cancer cells which express low but adequate levels of TLR3 protein engages polyI:C, which in turn activates TLR3-mediated caspase 3/8 apoptosis pathway. Single treatment with polyI:C alone suppresses survival, oncogenicity and metastatic potential of lung cancer cells (e.g. A549, NCI-H292). In addition to apoptosis, polyI:C increases the secretion of IL6 through activation of STAT3 and JAK2. A combinatorial treatment with polyI:C and anti-IL6 antibody decreases IL6 production and subsequently enhances the polyI:C-killing and suppresses oncogenicity and metastatic potential of A549. Similarly, blockade of STAT3 and JAK2 activities by Stattic and AG490 antagonists, respectively, enhances the cancer killing effect of polyI:C. Taken together, a combinatorial treatment of polyI:C+anti-IL6 enhances the impact of polyI:C-killing of A549 through IL6/JAK2/STAT3 signalling pathway.