Objective This study aimed to investigate expressions and clinical significance of IL-17 and TNF-alpha after surgery in patients with Hashimoto's disease (HD) combined with thyroid cancer (TC). Patients and methods From June 2010 to October 2012, 38 patients with HD combined with TC admitted to the oncology department of Tongji Hospital were selected as an experimental group, including three males and 35 females, aged 24-78 years. Forty adults undergoing physical examination during the same period were selected as a control group. All patients in the experimental group were given total endoscopic TC resection. Real-time fluorescence quantification (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of serum IL-17 and TNF-alpha before and 14 days after surgery. Patients with HD combined with TC were divided into high and low expression groups according to the median values of preoperative IL-17 mRNA and TNF-alpha mRNA. The relationship between IL-17, TNF-alpha, and prognosis of patients was analyzed through K-M survival curve. Results The concentrations of IL-17 and TNF-alpha in serum were also higher than those in control group 14 days after surgery (p < 0.05). qRT-PCT showed that the relative expressions of IL-17 and TNF-alpha in serum 14 days after surgery were higher than those in control group (p < 0.05). According to the relative expression median of mRNA in IL-17 and TNF-alpha before surgery, they were divided into high and low expression groups. It was found that the survival rate of high expression groups of IL-17 and TNF-alpha was lower than that of low expression groups (IL-17, p = 0.028; TNF-alpha, p = 0.014). Conclusions The protein and mRNA of IL-17 and TNF-alpha in serum of HD patients with TC are higher than those of healthy control group. Expressions of IL-17 and TNF-alpha can be reduced by surgical resection of focal tissue. IL-17 and TNF-alpha may be used as potential prognostic indicators of HD patients with TC.