Ovarian cancer is a type of gynecological cancer with the highest mortality rate worldwide. Due to a lack of effective screening methods, most cases are diagnosed at later stages where the survival rates are poor. Thus, it is termed a ‘silent killer’ and is the most lethal of all the malignancies in women. IQ motif containing GTPase Activating Protein 3 (
IQGAP3
) is a member of the Rho family of GTPases, and plays a crucial role in the development and progression of several types of cancer. The aim of the present study was to investigate the oncogenic functions and mechanisms of
IQGAP3
on the proliferation and metastasis of high-grade serous ovarian cancer (HGSOC). Therefore, the expression levels of
IQGAP3
in HGSOC and normal tissue samples were compared, and
IQGAP3
knockdown was performed to examine its functional role using various
in vitro
and
in vivo
experiments. It was demonstrated that the expression of
IQGAP3
was upregulated in HGSOC tissues compared with the healthy tissues; this differential expression was also observed in the ovarian cancer cell lines. Functional experimental results suggested that
IQGAP3
silencing significantly reduced proliferation, migration and invasion in ovarian cancer cell lines. Moreover,
in vivo
experimental findings validated the
in vitro
results, where the tumorigenic and metastatic capacities of
IQGAP3
-silenced cells were significantly lower in the nude mice compared with the mice implanted with the control cells. Furthermore, knockdown of
IQGAP3
resulted in increased apoptosis, and the effects of
IQGAP3
expression on various epithelial-mesenchymal transition markers were identified, suggesting a possible mechanism associated with the role of
IQGAP3
in metastasis. The effect of
IQGAP3
silencing on chemosensitivity towards olaparib was also assessed. Collectively, the present results indicated that
IQGAP3
is a potential diagnostic and prognostic marker, and a putative therapeutic target of HGSOC.