Highly porous surface fluorinated SnO2 hollow nanospheres (SnO2(F) HNS) were produced in high yield by a hydrothermal treatment of stannous fluoride in the presence of hydrogen peroxide. Two important processes in terms of oriented self-assembly and in situ self-transformation were highlighted for the formation of as-prepared SnO2(F) HNS, which were largely relying on the directing effects of selected specific chemical species in the present synthesis system. Significantly, these SnO2(F) HNS showed considerable activity in photocatalytic inactivation of a surface negatively charged bacterium, Escherichia coli K-12, in aqueous saline solution. The dominant reactive species involved in the inactivation process were also identified.