In past decade of rapid industrial development and urbanization, China has witnessed increasingly persistent severe haze and smog episodes, posing serious health hazards to the Chinese population, especially in densely populated cities. Quantification of health impacts attributable to PM2.5 (particulates with aerodynamic diameter ≤ 2.5 μm) has important policy implications to tackle air pollution. The Chinese national monitoring network has recently included direct measurements of ground level PM2.5, providing a potentially more reliable source for exposure assessment. This study reports PM2.5-related long-term mortality of year 2015 in 161 cities of nine regions across China using integrated exposure risk (IER) model for PM2.5 exposure-response functions (ERF). It further provides an estimate of the potential health benefits by year 2020 with a realization of the goals of Air Pollution Prevention and Control Action Plan (APPCAP) and the three interim targets (ITs) and Air Quality Guidelines (AQG) for PM2.5 by the World Health Organization (WHO). PM2.5-related premature mortality in 161 cities was 652 thousand, about 6.92% of total deaths in China during year 2015. Among all premature deaths, contributions of cerebrovascular disease (stroke), ischemic heart disease (IHD), chronic obstructive pulmonary disease (COPD), lung cancer (LC) and acute lower respiratory infections (ALRIs) were 51.70, 26.26, 11.77, 9.45 and 0.82%, respectively. The premature mortality in densely populated cities is very high, such as Tianjin (12,533/year), Beijing (18,817/year), Baoding (10,932/year), Shanghai (18,679/year), Chongqing (23,561/year), Chengdu (11,809/year), Harbin (9037/year) and Linyi (9141/year). The potential health benefits will be 4.4, 16.2, 34.5, 63.6 and 81.5% of the total present premature mortality when PM2.5 concentrations in China meet the APPCAP, WHO IT-1, IT-2, IT-3 and AQG respectively, by the year 2020. In the current situation, by the end of year 2030, even if Chines government fulfills its own target to meet national ambient air quality standard of PM2.5 (35 μg/m3), total premature mortality attributable to PM2.5 will be 574 thousand across 161 cities. The present methodology will greatly help policy makers and pollution control authorities to further analyze cost and benefits of air pollution management programs in China.