This research focuses on extraction of medicinal plant Launaea acanthodes (L. acanthodes) by using supercritical carbon dioxide (SC-CO2) and hydro-distillation (HD) methods. The influence of pressure, temperature, flow rate and volume of co-solvent on the extraction yield of L acanthodes was investigated by response surface methodology (RSM) and artificial neural network (ANN). The error values of RSM (R-2 = 0.9871, MSE = 0.000016 and AARD = 2.395) and ANN (R-2 = 0.9968, MSE= 0.0000057 and AARD = 1.301) were calculated. The results exhibited that both models have the ability to predict the experimental data, but ANN was more reliable than the RSM. The maximum extraction yield was estimated by RSM to be 1.0250% under the operational conditions of pressure 240 bar, temperature 328 K, flow rate 4.06 g/min and co-solvent 663 mu l; whereas the optimum extraction yield estimated by hybrid ANN-GA method was 1.0238% applying the operational conditions of pressure 240 bar, temperature 328 K, flow rate 3.98 gimin and co-solvent 650 mu l. The maximum yield (1.0238%) obtained at the optimal conditions was more than that achieved by hydro-distillation method (0.7530%). The extracted components obtained from both methods were analyzed by GC/MS and GC-FID. The main compounds found in the extracts were gamma-Phenylbutyric acid (9.29, 9.19%), Geranyl acetone (7.67, 7.87%), n-Hexadecane (7.34,6.26%), (Z)-3-Hexen-1-yl-benzoate (7.10,6.91%), n-Dodecanal (5.87,6.56%), (2Z,6E)-Farnesol (5.65, 4.34%) and Benzoic acid n-hexyl ester (5.13,4.51%) and beta-lonone (4.55,4.58%) for SC-CO2 and HD methods, respectively. To the best of our knowledge, this is the first report on the extraction of essential oil from L. acanthodes. (C) 2016 Elsevier B.V. All rights reserved.