The management of papillary thyroid carcinoma (PTC) concurrent with Hashimoto's thyroiditis (HT) lacks standardized guidelines, especially concerning surgical strategies. This study aimed to compare unilateral thyroidectomy (UT) with total thyroidectomy (TT) in PTC-HT patients to optimize clinical management and improve postoperative outcomes. This retrospective study included PTC-HT patients undergoing thyroid surgery at a tertiary academic medical institution from January 2018 to August 2023. The patients were grouped according to the quartiles of preoperative thyroid peroxidase antibody (TPOAB) levels at the last follow-up. Additionally, patients were divided into UT and TT groups, with propensity score matching (PSM) to ensure comparability. Patients were also stratified by TPOAB levels (L: 100-400, M: 400-1000, H: >1000). Patient-reported outcomes (PROMs), including quality of life and fatigue, were compared between UT and TT groups within each TPOAB subgroup (ΔPROMs = UT-TT). 246 patients were included. Those with higher TPOAB levels at the last follow-up reported increased physical fatigue scores. After PSM, there were no significant demographic differences between UT and TT groups. During a median follow-up of 16 months for UT and 20 months for TT, no recurrence or metastasis occurred. Compared to the UT group, the TT group exhibited lower TPOAB levels at the last follow-up (65.7 ± 78 vs. 374.6 ± 331.9, p < 0.001), and lower physical fatigue scores (3.6 ± 2.5 vs. 4.5 ± 2.8, p = 0.039). However, TT was associated with a higher incidence of transient hypoparathyroidism (7.8% vs. 1.1%, p = 0.030). Stratified analysis by preoperative TPOAB levels revealed significant differences in ΔPROMs (Physical fatigue) between L and H groups (0.2 ± 3.5 vs. 4.6 ± 2, p = 0.004) and between M and H groups (0.6 ± 4.5 vs. 4.6 ± 2, p = 0.037). ΔPROMs (Mental fatigue) also significantly differed between L and H groups (0 ± 1.8 vs. 1.6 ± 0.9, p = 0.026). For PTC-HT patients, particularly those with high preoperative TPOAB levels, TT offers advantages in alleviating fatigue symptoms but carries a higher risk of complications. Therefore, clinical decision-making should consider patient-specific factors, particularly preoperative TPOAB levels, to determine the optimal surgical approach.Trial registration: Chinese Clinical Trial Registry. ID ChiCTR2300069240.