Nanoscale alpha-MnO2 with different morphologies (nanoparticles, nanoflowers and nanorods) were synthesized via a facile hydrothermal method and tested in peroxymonosulfate (PMS) activation for ciprofloxacin (CIP) degradation. The catalytic activity of alpha-MnO2 mainly relied on the specific surface area and crystallinity, and followed the order of alpha-MnO2 nanoflowers > alpha-MnO2 nanorods > alpha-MnO2 nanoparticles > commercial MnO2. Acidic condition was more beneficial to CIP removal than neutral condition, and the degradation would be greatly accelerated in alkaline circumstance. The introduction of chloride and bicarbonate displayed concentration-dependent dual effect. The presence of natural organic matter (NOM) exerted the detrimental effect on CIP degradation. Eleven oxidation products were identified by UPLC-MS/MS and the changes of their concentrations were monitored, five products showed monotonous uptrend while four intermediates present monotonous downtrend once they were generated. Piperazine ring cleavage, hydroxylation and F/OH substitution were found to be the important oxidation pathways. The acute toxicity of resulted solution gradually decreased with the lapse of time, and higher PMS concentration favored the detoxification. The CIP removal in alpha-MnO2/PMS process was also efficient under the actual water background, which was testified by the results of fluorescence excitation-emission matrix (EEM).