To continue the quest of newer anticancer agents, herein a novel class of 1,4-Dihydroindenopyrazole linked oxadiazole conjugates 9(a-r) was designed, synthesized and experimented for their anti-proliferative activities against four different cancer cell lines (human) such as MDA MB-231 (breast), PANC-1 (pancreatic), MCF-7 (breast), and Caco-2 (Colorectal) by using MTT assay. Among the series compound 9h and 9 m demonstrated significant potency against the PANC-1 (human pancreatic cancer cells) with IC<sub>50</sub> value 7.4 μM and 4.3 μM respectively. While compound 9 m was found to be equipotent to standard Gomitabine (IC<sub>50</sub> = 4.2 μM). The detailed biological assays revealed S phase cell cycle arrest and their ability to propagate apoptosis by activating caspase 3 and 9 enzymes which was confirmed by Annexin-FITC assay and caspase assay. Moreover, docking study suggested their binding modes and interactions with caspase-3. In addition, in silico studies revealed that they exhibit good pharmacokinetics and drug likeliness properties. Furthermore, 3D-QSAR was carried out to achieve a pharmacophoric model with CoMFA (q<sup>2</sup> = 0.631, r<sup>2</sup> = 0.977) and CoMSIA (q<sup>2</sup> = 0.686, r<sup>2</sup> = 0.954) on PANC-1 cancer cells which were established, generated and validated to be reliable models for further design and optimization of newer molecules with enhanced anticancer activity.