This study aimed to evaluate differential apoptotic response in uterine cervical cancer cells with and without HPV infection after chemotherapy. CaSki (HPV 16-positive) and C33A (mutant p53 and HPV-negative) cells were used. Cell viability was assessed by trypan blue cell exclusion test. Apoptosis was evaluated by DNA fragmentation analysis and flow cytometric analysis. Differential apoptotic responses were evaluated using Western blot analysis after chemotherapy. Decreased cell viability and apoptosis were displayed in CaSki and C33A cells after chemotherapy using doxorubicin (DOX). Regarding apoptosis-related molecules, the appearance of cleaved PARP expression was more prominent in CaSki cells. p53 and p21 expression in CaSki cells were increased. On the other hand, JNK expression was different in C33A cells (increased) and CaSki cells (decreased). CaSki cells and C33A cells showed differential apoptotic responses after chemotherapy using DOX. CaSki cells seem to be related with p53/p21 expression, but C33A cells seem to be related with PARP-JNK expression, which is involved in the mitochondrial pathway.