Essential (volatile) oil from aerial parts of Tamarix aphylla (L.) H.Karst. (Tamaricaceae) grown wild in Jordan was hydrodistilled by Clevenger apparatus and analyzed by means of GC and GCâMS techniques. In vitro screening of potential cytotoxicity of the aqueous (AE) and ethanol (EE) extracts was also evaluated against human breast adenocarcinoma (MCFâ7), colorectal adenocarcinoma (Cacoâ2), and pancreatic carcinoma (Pancâ1) cancer cell lines as well as normal human fibroblasts. GCâMS analysis of T. aphylla EO revealed its richness in nonterpenoid nonaromatic hydrocarbons (52.39%), with predominance of 6,10,14âtrimethylâ2âpentadecanone as the principal component. Biologically, the plant extracts exhibited cytotoxicity effects in doseâdependent manner against most of the tested cell lines, but potent effects were only predicted against MCFâ7 cells with IC 50 values of 2.17 ± 0.10 and 26.65 ± 3.09 μ g/mL for T. aphylla AE and EE, respectively. T. aphylla AE demonstrated a comparable cytotoxic effect with that offered by the control drug cisplatin (IC 50 value of 1.17 ± 0.13 μ g/mL), even with higher safety profile against normal fibroblast cells (IC 50 values of T. aphylla AE versus cisplatin: 79.99 ± 4.90 versus 9.08 ± 0.29 μ g/mL). T. aphylla extracts could be a valuable source for cytotoxic agents with high safety and selective cytotoxicity profiles. Unfortunately, no antiproliferative potential against Cacoâ2 or Pancâ1 cancer cell lines was detected at a concentration less than 30 μ g/mL.