Chemokine (C-C motif) ligand 6 (CCL6), one of the small cytokines in the CC chemokine family, has been reported to involve in renal ischemia-reperfusion (I/R) injury. However, the role of CCL-6 in myocardial I/R injury is nonelucidated. In this study, we used in vitro H9c2 cell model to investigate the overall contributions of CCL6 to myocardial I/R injury. We found the elevated level of CCL6 from the reanalysis of data set GSE-4105 and in hypoxia-reoxygenation (H/R)-injured H9c2 cells. CCL6 silencing attenuated the cardiomyocyte apoptosis induced by H/R injury, whereas exogenous CCL6 treatment aggravated the apoptosis of H/R-injured H9c2 cells. During CCL6 administration, the expression of numerous long noncoding RNAs was differentially regulated. Quantitative RT-Polymerase chain reaction assay demonstrated that insulin-like growth factor 2 (IGF2)-Antisense (AS) had the highest induction by CCL6 addition. IGF2-AS silencing alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have identified a potential mechanism by which high expression of CCL6 contributes to the H/R-induced apoptosis in H9c2 cells through enhancing the expression of IGF2-AS. These findings also give evidence of the feasibility of CCL6 or long noncoding RNA IGF2-AS as a potential target for modulation or therapeutic intervention in myocardial I/R injury.