The polypyrrole modified loofah (PPy-Loof), a novel adsorbent, was prepared simply by in-situ oxidative polymerization of pyrrole onto loofah for effective removal of hexavalent chromium (Cr(VI)) from water. The preparation process of PPy-Loof was investigated, and the structure of prepared PPy-Loof was characterized by SEM-EDS, FT-IR, XRD, and XPS analysis. Batch experiments (the effect of temperature, initial Cr(VI) concentration, PPy-Loof dosage, and coexisting ions) were designed to investigate the adsorption. The Cr(VI) adsorption behaviors of PPy-Loof were analyzed by the isothermal models (Langmuir, Freundlich and Temkin), the kinetic models (Pseudo first-order kinetic, Pseudo second-order kinetic and Intra-particle diffusion models), and adsorption thermodynamics (Gibbs free energy change (ΔG0), entropy change (ΔS0), enthalpy change (ΔH0) and activation energy (Ea)). The Cr(VI) removal mechanism of PPy-Loof was further discussed by studying the influence of the initial pH in the solution, the pH changes of the solution during the process, the analysis of XPS, and the validation of the exchanged Cl− during the Cr(VI) removal. The results indicated PPy-Loof could not only effectively removed Cr(VI) from water, but also achieved in-situ detoxification of Cr(VI) by reduction to Cr(III). Adsorption progress conformed to the Langmuir isotherm and pseudo-second-order model, indicating the chemical and monolayer adsorption. ∆H0 > 0, ∆S0 > 0, ∆G0 < 0, indicated the spontaneous and endothermic progress of Cr(VI) adsorption on PPy-Loof. The electrostatic attraction, ion exchange interaction, as well the reduction effect, were supposed as the main mechanism of Cr(VI) removal by PPy-Loof.