Abstract: To study the relationships of routine leaf chemical components in medium flavor style flue-cured tobacco with the components in mainstream cigarette smoke, 31 tobacco leaf samples were collected from the planting areas of typical medium flavor style flue-cured tobacco in Guizhou, Chongqing, Shandong, Shaanxi and Heilongjiang. The correlations between the routine chemical components in tobacco leaves and the components in mainstream cigarette smoke were analyzed by correlation analysis, stepwise regression analysis and path analysis. The results showed that:1) The release of total particulate matter (TPM), CO and tar in mainstream cigarette smoke significantly negatively correlated to the potassium content and significantly positively correlated to the chlorine content in tobacco leaves. Moisture content in mainstream cigarette smoke significantly negatively correlated to the potassium and reducing sugar contents in tobacco leaves. 2) The potassium and protein contents in tobacco leaves were two important indexes affecting the release of TPM and CO in mainstream cigarette smoke; and the contents of total sugar, potassium and total nitrogen in tobacco leaves influenced the moisture content in mainstream cigarette smoke greatly, as did the contents of total nitrogen, potassium and protein to the tar yield in mainstream cigarette smoke. Path analysis indicated that the chemical components in tobacco leaves positively or negatively indirectly affected the components in mainstream cigarette smoke, it suggested that there were promotion or inhibition between the chemical components in tobacco leaves and the components in mainstream cigarette smoke. Therefore, the contents of total nitrogen, total sugar, potassium and protein in tobacco leaves of medium flavor style flue-cured tobacco make the greatest contribution to the components in mainstream cigarette smoke, and the harmony between different chemical components in tobacco leaves is important to the release of mainstream cigarette smoke.