This study aimed to investigate the roles of PALMD in ovarian cancer. mRNA expression was detected using RT-qPCR. The aldehyde dehydrogenase (ALDH) activity and biomarkers of ovarian cancer stem cells were determined using flow cytometry. The stemness of ovarian cancer cells was determined using sphere formation assay. Cell viability was determined using CCK-8 assay. The number of colonies was determined using colony formation assay. Cell migration was detected using wound healing assay. Cell invasion was determined using transwell assay. The results showed that PALMD was downregulated in ovarian cancer. Overexpressed PALMD inhibited the proliferative, migrative, and invasive ability of ovarian cancer cells. Moreover, PALMD inhibited the stem-like properties of ovarian cancer cells. Additionally, PALMD downregulated ring finger protein 145 (RNF145) expression, overexpression of which contributed to the aggressiveness of ovarian cancer cells. Taken together, PALMD suppressed ovarian cancer cell stem specification via inhibiting RNF145 expression.