Aim To investigate the influence of calcitonin gene-related peptide (CGRP) on the survival activity of c-kit^pos cardiac stem cells(c-kit⁺ CSC) in hypoxia, and research its potential mechanism. Methods c-kit⁺ CSC was obtained by enzyme digestion and immune magnetic bead separation. Then serum-free hypoxia model of c-kit⁺ CSC was established in vitro. The models were randomly divided into hypoxia group, CGRP+hypoxia group, CGRP+CGRP₈-37+hypoxia group and control group(no hypoxia). The activity of cells was detected by cell counting kit (CCK-8 kit),the apoptosis of cells were detected by flow cytometry(FCM) and mitochondrial membrane potential. Results Under hypoxia condition,compared with the control group,the activity of c-kit⁺ CSC was significantly decreased in the hypoxia group(P<0.05),but compared with the hypoxia group,the activity of c-kit⁺ CSC was significantly increased in CGRP+hypoxia group at different time points of CGRP effect on hypoxia cells(P<0.05), especially in 30 min and 60 min; When inhibiting the effect of CGRP on hypoxia, compared with CGRP+hypoxia group,the activity of c-kit⁺ CSC was significantly decreased in the CGRP+CGRP₈-37+hypoxia group at 30 min and 60 min after hypoxia(P<0.05). In terms of apoptosis, compared with the control group,the early apoptosis rate was the highest in hypoxia group(P<0.05); After CGRP treating c-kit⁺ CSC in hypoxia, we could find that CGRP+hypoxia group had a lower early apoptosis rate(P<0.05), when inhibiting the effect of CGRP on hypoxia, the early apoptosis rate was the highest in CGRP+CGRP₈-37+hypoxia group, but there was no significant difference in early apoptosis rate between hypoxia group and CGRP+CGRP₈-37+hypoxia group(P>0.05). Mitochondrial membrane potential showed, compared with the hypoxia group, red fluorescence and green fluorescence ratio increased in CGRP+hypoxia group(P<0.05), when inhibiting the effect of CGRP on hypoxia, compared with the CGRP+hypoxia, the red fluorescence and green fluorescence ratio decreased in CGRP+CGRP₈-37+hypoxia group(P<0.05). Conclusion CGRP can promote the proliferation and survival of c-kit⁺CSC under hypoxia, and inhibit the early apoptosis of the cell.