Chromosome 2p21 (gene locus of hMSH2) was amplified in OC3/TAX300 cells. hMSH2 was overexpressed in 93.9 and 47.6% of paclitaxel-treated and untreated ovarian carcinoma tissue samples (P=0.0001), respectively. hMSH2 was overexpressed in 93.3 and 54.2% of low-differentiated and moderate-to-highly differentiated ovarian carcinoma tissue samples (P=0.0008), respectively. hMSH2 expression was inhibited in the OC3/TAX300 cells transfected with hMSH2 siRNA. hMSH2 siRNA increased paclitaxel sensitivity, inhibited OC3/TAX300 cell proliferation (G2/M arrest), and increased susceptibility to apoptosis. hMSH2 expression was upregulated in ovarian carcinoma cell lines and tissues after paclitaxel treatment. hMSH2 overexpression is related to paclitaxel resistance and poor prognosis.