In the past decades, an extensive effort has been devoted to remove Hexavalent chromium H(Cr (VI)) from industrial effluents, owning to its great health concerns to humans and the environment. Recently, Metal organic framework (MOFs) adsorbents draws more attention of researchers to remove contaminants from aqueous environments in the recent years. In the present study, solvothermal method was employed to fabricate MOF-5 that was examined for Cr (VI) adsorption from water matrices. XRD, FESEM, EDS, FTIR and BET analyses were utilized to characterize MOF-5. The influence of some independent parameters on MOF-5 performance in Cr (VI) adsorption was explored in a batch mode system. It was found that the uptake rate of Cr (VI) is significantly affected by initial pH of solution; the maximum adsorption rate is favored by acidic pH. Also, the adsorption efficiency shows a direct relationship with contact time and adsorbent dose, and an indirect relation with initial Cr (VI) concentration. The adoption process was modeled and optimized successfully by two approach of response surface methodology and artificial neutral network approaches; both models indicated an accuracy of predictions by determining error distribution and statistical significance and a good fit to experimental data. The experimental data showed a superior agreement with linear and nonlinear Langmuir isotherm, as compared with the other isotherm models, and pseudo-second-order kinetic better described Cr (VI) adsorption data by MOF-5, compared to the other kinetic models. The maximum absorption capacity was 78.12 mg/g. Thermodynamic studies revealed that adsorption is spontaneous and endothermic process. The findings claimed the great reusability and high stability of MOF-5; adsorption efficiency decreased only by 92.4% after ten recycles. The interfering anions affected negatively on the adsorption efficiency in the order of phosphate > sulfate > chloride > nitrate. The present study provides valuable and good information for Cr (VI) adsorption on MOF-5 in water matrices.