Objective. To explore the clinical utility of tumor-specific growth factor (TSGF) and the soluble interleukin-2 (IL-2) receptor (sIL-2R) as immune-related factors for predicting lymph node metastases (LNM) of papillary thyroid carcinoma (PTC). Methods. A total of 206 patients with PTC subjected to curative surgery were enrolled. All patients had complete medical records. Serum levels of TSGF were detected using Automatic Biochemistry Analyzer and the serum sIL-2R concentration was detected by enzyme-linked immunosorbent assay (ELISA). Furthermore, we analyzed the relationship between the two indicators and the clinicopathological characteristics and assessed their effect on lymphatic metastasis in patients with PTC by logistic regression analysis. Results. Receiver operating characteristic (ROC) analysis revealed that the determined cut-off value of serum TSGF and sIL-2R was 63.35 U/mL and 507 U/mL, respectively. Serum TSGF was associated with focality (
χ
2
=
4.97
,
P
=
0.026
) and lymphatic metastasis (
χ
2
=
4.154
,
P
=
0.042
), while serum sIL-2R was remarkably related to gender (
χ
2
=
4.464
,
P
=
0.035
). Univariate logistic regression analysis indicated that age, tumor size, serum TSGF level, capsule invasion, and nodular goiter were the lymphatic metastasis-related factor of PTC. Multivariate regression analysis revealed that
age
>
45
years was a protective factor (OR: 0.4, 95% CI: 0.206-0.777,
P
=
0.007
). Conversely, larger tumor size (OR: 4.594, 95% CI: 2.127-9.921,
P
=
0.000
), higher serum TSGF levels (OR: 1.888, 95% CI: 1.009-3.533,
P
=
0.047
), and capsule invasion (OR: 1.939, 95% CI: 1.009-3.726,
P
=
0.047
) were associated with an increased risk of LNM. Conclusion. Serum TSGF levels were identified as an independent factor for LNM in patients with PTC.