As large-scale integrated circuit chips manufacturing steps into the era of tens of nanometers technology node, the focus control of the lithography machine becomes more and more difficult with the precision of several tens of nanometers. In this paper, a statistical analysis method of immersion lithography focusing control is studied based on the architecture and lithography focusing principle of actual lithography machine focusing control system. A series of error sources are obtained based on the system structure, and their contribution way and relationship to the total defocus error are investigated. The results show that due to the non-normal distribution error contribution term in lithography focusing error, the 3σ principle used in the normal statistical distribution can not meet the 99.7% focusing success rate requirement. In the manufacturing process of 28,14,7 nm technology node integrated circuit chips, the difference of the total focusing success rates of immersion lithography can be as high as 28.4%, 55.1% and 62.9%, when 3σ and 4σ principles are used respectively. In order to reach 99.7% focusing success rate, the 4σ principle should be used in the focus control of immersion lithography.