Objective: To examine the associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma, so as to provide insights into prevention of papillary thyroid carcinoma. Methods: Totally 57 patients with papillary thyroid carcinoma admitted to two tertiary hospitals in Urumqi, Xinjiang Uygur Autonomous Region in 2018 were selected as the case group, while 57 subjects with normal thyroid functions during the same period were selected as the control group. Subjects' gender, age, ethnicity, occupation and medical history of thyroid disease were collected using questionnaire surveys. Serum dimethyl arsenic acid (DMA) and monomethyl arsenic acid (MMA) were determined using high-performance liquid chromatography (HPLC) coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS), serum thyroid hormone (TSH) by radioimmunoassay, estradiol (E2) by enzyme-linked immunosorbent assay and estrogen receptor ERα and ERβ by western blotting. The associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma were evaluated using a multivariable logistic regression model. Results: There were 16 males (28.07%) and 41 females (71.93%) in the case group, with a mean age of (42.63±11.01) years, and there were 21 males (36.84%) and 36 females (63.16%) in the control group, with a mean age of (40.89±11.30) years. There were no significant differences between the case and control groups in terms of age (χ2=0.373, P=0.542), gender (χ2=1.000, P=0.317) or ethnic composition (χ2=0.291, P=0.590). The serum levels of TSH [2.85 (1.61) vs. 2.45 (1.79) μmol/L], E2 [74.93 (120.44) vs. 61.60 (37.35) pmol/L], ERα [1.49 (1.13) vs. 0.70 (0.31)], ERβ [1.59 (0.55) vs. 0.72 (0.36)], DMA [116.02 (100.48) vs. 32.33 (56.06) μg/L] and MMA [56.92 (47.90) vs. 27.90 (24.99) μg/L] were all significantly higher in the case group than in the control group (Z=-2.414, -2.292, -4.923, -5.167, -5.448 and -4.019, all P<0.05). Multivariable logistic regression analysis showed DMA (OR=1.013, 95%CI: 1.003-1.024) and E2 levels (OR=1.020, 95%CI: 1.004-1.036) were associated with the risk of papillary thyroid carcinoma. Conclusion Increased arsenic load and elevated estradiol levels may be associated with the risk of papillary thyroid carcinoma.