Polyaniline/sepiolite (PANI/sepiolite) nanofibers were prepared by in situ chemical oxidation polymerization in the presence of sepiolite. The effect of aniline/sepiolite weight ratio on the nanostructure of PANI/sepiolite composites was investigated by field-emission scanning electron microscopy. The adsorption of Cr(VI) onto the PANI/sepiolite nanofibers was highly dependent on pH values. The pseudo-second-order and Langmuir isothermal models can well describe the adsorption kinetics and adsorption isotherm, respectively. The maximum adsorption capacity of the PANI/sepiolite nanofibers for Cr(VI) was up to 206.6 mg/g at 25 °C and increased with the increase in temperature. Desorption experiments indicated that PANI/sepiolite can be regenerated and reused for two consecutive cycles with no loss of its removal efficiency. PANI/sepiolite nanofibers can be used as a highly efficient and economically viable adsorbent for Cr(VI) removal due to their excellent adsorption characteristics.