The present study investigates whether the chronic low-dose radiation exposure induces an in vivo radio-adaptive response in individuals from high-level natural radiation areas (HLNRA) of the Kerala coast. Peripheral blood samples from 54 adult male individuals aged between 26 and 65 years were collected for the study with written informed consent. Each of the whole blood sample was divided into three, one was sham irradiated, second and third was exposed to challenging doses of 1.0 and 2.0 Gy gamma radiation, respectively. Cytokinesis-block micronucleus (CBMN) assay was employed to study the radio-adaptive response. Seventeen individuals were from normal-level natural radiation area (NLNRA ≤1.5 mGy/year) and 37 from HLNRA (> 1.5 mGy/year). Based on the annual dose received, individuals from HLNRA were further classified into low-dose group (LDG, 1.51–5.0 mGy/year, N = 19) and high-dose group (HDG >5.0 mGy/year, N = 18). Basal frequency of micronucleus (MN) was comparable across the three dose groups (NLNRA, LDG and HDG, P = 0.64). Age of the individuals showed a significant effect on the frequency of MN after challenging dose exposures. The mean frequency of MN was significantly lower in elder (>40 years) individuals from HDG of HLNRA as compared to the young (≤40 years) individuals after 1.0 Gy (P < 0.001) and 2.0 Gy (P = 0.002) of challenging doses. However, young and elder individuals within NLNRA and LDG of HLNRA showed similar frequency of MN after the challenging dose exposures. Thus, increased  level of chronic low-dose radiation (>5.0 mGy/year) seems to act as a priming dose resulting in the induction of an in vivo radio-adaptive response in elder individuals of the Kerala coast.