Orthodontic root resorption (ORR) is one of the serious adverse events related to orthodontic treatment. Caspases are important effector molecules that mediate the process of apoptosis. However, the relationship between the mechanism underlying ORR and apoptosis in the cementum has not been clarified. In this study, human cementoblast-like cells (HCEMs) were cultured and subjected to pressure conditions assumed during orthodontic tooth movement in vitro. We then examined the effect of compressive force on caspase 3, caspase 8, receptor activator of nuclear factor κ-B ligand (RANKL) and osteoprotegerin (OPG) release. Furthermore, the association between root resorption and caspase was examined using z-VAD-fmk, a caspase inhibitor. In addition, we used HCEMs to examine the expression of caspase 3, caspase 8, RANKL and OPG under heavy force (HF) or optimum force (OF) in vitro. We then assessed the effects of HF with caspase inhibition using z-VAD-fmk [heavy force+inhibition (HI) group] on RANKL release from HCEMs. The application of HF induced higher levels of caspase 3 and 8 than OF. RANKL expression in cementoblasts was observed after the release of caspase 3 and 8 in the HF group. RANKL expression was significantly decreased protein production was suppressed in the HI group compared with the HF group (p < 0.05). The RANKL/OPG ratio was significantly decreased to about 57% at 9 h and 40% at 12 h in the HI group compared with the HF group (p < 0.05). These findings suggest that cementoblasts produce caspase 3 and 8 under HF conditions to activate the apoptotic pathway and then induce osteoclasts via RANKL. We considered that it as part of the mechanism involved in ORR.