Objective To observe potential effect of radon hot springs on the changes of cell cycle and its regulatory proteins of CDK1,CDK2,CDK4,CDK6,CyclinD1,CyclinE1,WEE1,CDC25A in the peripheral blood lymphocytes of residents.Methods A random sampling method was used to persons 46 persons from the residents around radon hot spring in Wentang town,and 39 persons were selected from the control area without radon exposure.Flow cytometry was used to detect the changes of cell cycle and the expressions of cell cycle-related regulatory proteins.Multiple linear regression method was used to analyze the relationship between the expressions of cell cycle regulatory proteins and radon exposure.Results The percentages of cells at G0/G1 phase and S phase in lymphocytes were different in the two groups (t =2.250,-2.382,P ＜ 0.05).The expression levels of CDK1,CDK6 and CyclinE1 in the peripheral blood lymphocytes of radon hot spring group were significantly decreased (t =4.770,11.419,5.238,P ＜ 0.05) and negatively correlated with radon exposure (t =-5.097,-11.128,-5.117,P ＜0.05).The expression levels of CDK2,CDK4,CyclinD1,WEE1 and CDC25A in the peripheral blood lymphocytes of radon hot spring group were increased but not significantly(P ＞ 0.05).Conclusions The incidences of a higher ratio of S-phase cells and lower expression levels of CDK1,CDK6 and CyclinE1 in the peripheral blood lymphocytes of residents in Wentang town may be related to long-term radon exposure.