Background: Human exposure to silica dust is very common in both working and living environments. However, the potential long-term health effects have not been well established across different exposure situations. Methods and Findings: We studied 74,040 workers who worked at 29 metal mines and pottery factories in China for 1 y or more between January 1, 1960, and December 31, 1974, with follow-up until December 31, 2003 (median follow-up of 33 y). We estimated the cumulative silica dust exposure (CDE) for each worker by linking work history to a job-exposure matrix. We calculated standardized mortality ratios for underlying causes of death based on Chinese national mortality rates. Hazard ratios (HRs) for selected causes of death associated with CDE were estimated using the Cox proportional hazards model. The population attributable risks were estimated based on the prevalence of workers with silica dust exposure and HRs. The number of deaths attributable to silica dust exposure among Chinese workers was then calculated using the population attributable risk and the national mortality rate. We observed 19,516 deaths during 2,306,428 person-years of follow-up. Mortality from all causes was higher among workers exposed to silica dust than among non-exposed workers (993 versus 551 per 100,000 person-years). We observed significant positive exposure-response relationships between CDE (measured in milligrams/cubic meter-years, i.e., the sum of silica dust concentrations multiplied by the years of silica exposure) and mortality from all causes (HR 1.026, 95% confidence interval 1.023-1.029), respiratory diseases (1.069, 1.064-1.074), respiratory tuberculosis (1.065, 1.059-1.071), and cardiovascular disease (1.031, 1.025-1.036). Significantly elevated standardized mortality ratios were observed for all causes (1.06, 95% confidence interval 1.01-1.11), ischemic heart disease (1.65, 1.35-1.99), and pneumoconiosis (11.01, 7.67-14.95) among workers exposed to respirable silica concentrations equal to or lower than 0.1 mg/m 3. After adjustment for potential confounders, including smoking, silica dust exposure accounted for 15.2% of all deaths in this study. We estimated that 4.2% of deaths (231,104 cases) among Chinese workers were attributable to silica dust exposure. The limitations of this study included a lack of data on dietary patterns and leisure time physical activity, possible underestimation of silica dust exposure for individuals who worked at the mines/factories before 1950, and a small number of deaths (4.3%) where the cause of death was based on oral reports from relatives. Conclusions: Long-term silica dust exposure was associated with substantially increased mortality among Chinese workers. The increased risk was observed not only for deaths due to respiratory diseases and lung cancer, but also for deaths due to cardiovascular disease.