The anaerobic ammonium oxidation (anammox) process has the advantages of a high nitrogen removal rate, low operational cost, and small footprint and has been successfully implemented to treat high-content ammonium wastewater. However, very little is known about the toxicity of the heavy metal element Ni(II) to the anammox process. In this study, the short- and long-term effects of Ni(II) on the anammox process in an upflow anaerobic sludge blanket (UASB) reactor were revealed. The results of the short-term batch test showed that the half maximal inhibitory concentration (IC) of Ni(II) on anammox biomass was 14.6 mg L. A continuous-flow experiment was performed for 150 days of operation, and the results illustrated that after domestication, the achieved nitrogen removal efficiency was up to 93±0.03% at 10 mg L Ni(II). The settling velocity, specific anammox activity and EPS content decreased as the Ni(II) concentration increased. Nevertheless, the content of heme c increased as the Ni(II) increased. These results indicate that short-term exposure to Ni(II) has an adverse impact on anammox process, but the anammox system could tolerate 10 mg L Ni(II) stress after acclimation during continuous-flow operation for 150 days. High-throughput sequencing results indicated that the presence of Ni(II) had an impact on the microbial community composition in the anammox reactor, especially Candidatus Kuenenia. At Ni(II) concentrations of 0-10 mg L, the relative abundance of Candidatus Kuenenia decreased from 36.23% to 28.46%.