The current measures of cognitive functioning in adulthood do not indicate a long-term association with prenatal exposure to the Dutch famine. However, whether such association emerges in China is poorly understood. We aimed to investigate the potential effect of prenatal exposure to the 1959-1961 Chinese famine on adult cognitive impairment. We obtained data from the Second National Sample Survey on Disability implemented in thirty-one provinces in 2006, and restricted our analysis to 387 093 individuals born in 1956-1965. Cognitive impairment was defined as intelligence quotient (IQ) score under 70 and IQ of adults was evaluated by the Wechsler Adult Intelligence Scale - China Revision. Famine severity was defined as excess death rate. The famine impact on adult cognitive impairment was estimated by difference-in-difference models, established by examining the variations of famine exposure across birth cohorts. Results show that compared with adults born in 1956-1958, those who were exposed to Chinese famine during gestation (born in 1959-1961) were at greater risk of cognitive impairment in the total sample. Stratified analyses showed that this effect was evident in males and females, but only in rural, not in urban areas. In conclusion, prenatal exposure to famine had an enduring deleterious effect on risk of cognitive impairment in rural adults.