Ovarian cancer (OC) is typically diagnosed at late stages, leading to low survival rates. In Australia, only 35% of OC patients survive 5 years after diagnosis. A common barrier to recovery is resistance to platinum-based chemotherapy (platinum-resistance). Platinum therapies intercalate in the DNA, making adducts that disrupt cell processes and lead to apoptosis. Several studies found that CLU (clusterin) is overexpressed in platinum-resistant OC. This study aimed to validate the knockdown of CLU and then assess the impact of CLU suppression on platinum sensitivity in OC. To achieve these aims, small interfering RNA (siRNA) targeting CLU mRNA was used to silence clusterin expression in OVCA-432 and OVCAR-3 OC cell lines and sensitivity to platinum was assessed using cell viability assays. The two major clusterin isoforms (secreted, sCLU and nuclear, nCLU) have opposing roles. sCLU is anti-apoptotic, whereas nCLU is apoptotic. The CLU targeted siRNA (CLU-siRNA) and the quantitative PCR primers used both targeted regions common to both isoforms. Carboplatin, a platinum-based chemotherapy, was administered to two OC cell lines with CLU-siRNA-treated cells, non-targeting siRNA-treated cells and a no-treatment control group. Both cell lines saw an increase in their half-maximal inhibitory concentration (IC50). This increased resistance was unexpected, as the hypothesis was that the IC50 would decrease. The supposed predominant isoform was the anti-apoptotic sCLU; therefore, reducing sCLU would logically increase sensitivity and lower the carboplatin required to achieve apoptosis. Although unexpected, this finding opens questions about the isoform levels of OC cell lines and the true nature of the isoforms, and it warrants further investigation into the function and relationship of clusterin with platinum therapies in OC.