The aim of this study was to determine whether pretreatment status of human epidermal growth factor receptor-2 (HER-2) could predict pathologic response to neoadjuvant chemoradiotherapy (nCRT) and outcomes for patients with locally advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC received standardized multimodal treatment. Their HER-2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. Twenty-two cases in 119 patients assessed as IHC3+ or IHC2+ plus gene-amplified were determined as HER-2 positive. Positive HER-2 status was not associated with any pretreatment clinicopathologic parameters (P > 0.05). HER-2 status could not predict pathologic response to nCRT based on downstaging (P = 0.210) and tumor regression grade (P = 0.085) but it provides us with a trend that HER-2-positive tumors may be resistant to nCRT. Positive HER-2 status was significantly associated with poor 5-year disease-free survival (P = 0.015) and 5-year overall survival (P = 0.026). It can act as a worse prognostic factor for LARC patients.