Water pipe (nargile) smoking is highly prevalent in developing countries, especially in the Eastern Mediterranean countries. It has been claimed that more than 100 million people smoke Water-pipe. Tobacco smoking is one of the leading behavioural factors related to an increased risk of cancer, one of the leading causes of death globally. This study aimed to innovate a novel filtration system for water-pipe smoke and evaluate the cytotoxic effect of common water-pipe condensed smoke in comparison with the novel filtration system on normal (HEK293t) and cancer cell lines (Hep3B and MCF7) by MTS assay, alpha-fetoprotein (aFP), and apoptosis/necrosis effects. Furthermore, the smoke substituents' neurotoxicity effect was evaluated by analysing the depressive property on AMPA receptors (AMPARs). The results proved that water can filtrate toxins, and by introducing silica filtration system we were able to reduce the quantity of toxic compounds from 145mg in distilled water extract (DWE) to 57.5 mg in silica solution extract (SSE). However, the SSE showed lower toxicity on different cell lines HEK293t Hep3B and MCF7 with CC50 values 149.9, 10.14 and 8.9 µg/ml, than DWE CC50 values 77.1, 3.1, and 5.24 µg/ml, respectively, as well as SSE reduced the α-FP to 2273.3 ng/ml which is closer values to untreated cells (4066.7 ng/ml) in comparison with DWE which reduced it greatly to 1658.7 ng/ml, and the biophysical properties of AMPAR subunits demonstrate a reduced effect on desensitization rates of GluA2 homomer and GluA1/2 heteromer, using SSE relative to DWE. In conclusion, the condensed smoke of ordinary water pipe (DWE) has cytotoxic and neurotoxic impacts on various cell lines, while our newly developed system (SSE) was less toxic.