Calcium (Ca2+) homeostasis is disrupted during aging in several cell types and this disruption leads to autophagy impairment. The mechanisms regarding Ca2+, senescence, and autophagy need to be elucidated. Therefore, we hypothesized that cellular senescence can be improved by regulating Ca2+ level and autophagy activity. We identified that hydrogen peroxide (H2O2)-induced senescence was accompanied by Ca2+ elevation, impairment of autophagic flux and increase of mammalian target of rapamycin (mTOR) phosphorylation in VSMCs. The treatment of nifedipine dose-dependently suppressed H2O2-induced senescence by reducing Ca2+ entry, autophagy impairment and mTOR signaling, and this suppression was found to be related to senescence-associated β-galactosidase (SA-β-gal) activity and the expressions of senescence marker protein 30 (SMP30), p53, and p21. Furthermore, H2O2-induced autophagy impairment also accelerated senescence and accumulations of ubiquitinated proteins. AMPK inhibition or transfection with AMPK siRNA showed that the anti-senescence effect of nifedipine involved AMPK activation. These results suggest nifedipine-inducted AMPK activation suppresses VSMC senescence by regulating autophagic flux and Ca2+ levels.