The toxicity of hexavalent chromium (Cr(VI)) is one of the challenges in implementing Anammox process to ammonium-rich wastewater treatment. However, the response of Anammox process to Cr(VI) stress and the inhibition mechanism remain unclear. Here, two Anammox UASB reactors were operated for 285 days under different Cr(VI) stresses. The results showed Anammox performance was not affected at low Cr(VI) concentration (i. e., 0-0.5 mg L-1), but was severely inhibited at 0.8 mg L-1. Attempts to domesticate Anammox process to higher Cr(VI) by lowering nitrogen loading rate were failed. Examination of Cr(VI) fate showed the occurrence of extracellular and intracellular Cr(VI) reduction to Cr(III). The inhibition was ascribed to the significant intracellular Cr(VI) reduction, accounting for 99.78% of the total Cr(VI) reduction. Moreover, under long-term Cr (VI) exposure, most nitrite was oxidized to nitrate. But microbial community showed no enrichment of Cr(VI) reducing bacteria and other nitrogen transformation-related bacteria.