One of the common causes of cancer-related mortalities worldwide is lung cancer and more than 1 million people annually die from it. Lung cancers are divided into Non-small cell lung cancer (NSCLC) and small cell lung carcinomas (SCLCs) which are different in several characteristics like biological behavior, response to therapy and genetic alterations.

Resistance to conventional chemotherapy, especially in NSCLC patients is a major challenge in the treatment process. Therefore, development of novel therapeutic strategies is essential for improvement of survival rate. Combination of different therapeutic methods is an approach which can maximize efficiency of the treatment.

Small interfering RNA (siRNA) has been reported to have a huge potential for the treatment or prevention of various lung diseases. Once the RNA molecules have successfully entered the target cells, they could inhibit the expression of specific gene sequence through RNA interference (RNAi) mechanism and generate therapeutic effects. The biggest obstacle to translating siRNA therapy from the laboratories into the clinics is delivery. An ideal delivery system should protect the siRNA from enzymatic degradation, facilitate cellular uptake and promote endosomal escape inside the cells, with negligible toxicity.

Very limited work has been done on the formulation of siRNA for inhalation which is believed to be the direction for future development. This review article introduces lung cancer and siRNA as a new treatment, and also studies the challenges of siRNA delivery to lung cells by non-viral carriers. Furthermore, it surveyed some nano carriers for pulmonary siRNA delivery with lipid, polymer and peptide basic.