Organic micropollutants (MPs) in low concentrations can affect aquatic ecosystems and human health. Adsorption technique is one of the promising methods to remove MPs. Chitosan and zeolites are environmentally friendly and low-cost adsorbents. Thus, removal of organic MPs (such as bisphenol A (BPA), carbamazepine (CBZ), ketoprofen (KTF) and tonalide (TND) from aqueous solution via cross-linked chitosan/zeolite, as a fixed-bed column, was investigated in the current study. Hydraulic retention time was set at 0.8 h pH and concentration of organic MPs ranged from 4 to 8 and 0.50 mg/L to 2.0 mg/L, and they were considered as factors in optimizing the removal of pollutants via response surface methodology (RSM). Approximately 1.4560 mg/L (89.0%) of BPA, 1.4724 mg/L (90.0%) of CBZ, 1.4920 mg/L (91.2%) of KTF and 1.4118 mg/L (86.3%) of TND were removed at 5.1 pH and 1.636 mg/L initial concentration as the optimum removal efficiency on the basis of RSM. Artificial neural network (ANN) was used to optimise removal effectiveness for each MP. The high R values and reasonable mean squared errors indicated that ANN optimized MP removal in a logical aspect. Adsorption isotherm studies revealed that organic MP removal through chitosan/zeolite could be explained with Freundlich and Langmuir isotherms.