The way to monitor tuberculosis (TB) treatment is extremely lacking in clinical practice. The aim of the study is to assess the role of the TBAg/PHA ratio in the treatment monitoring of TB. TB patients were followed up for 6 months and serial T-SPOT.TB (T-SPOT) assays were performed. In patients with successful treatment outcomes, the ESAT-6 sfc, CFP-10 sfc, and TBAg/PHA ratio all showed a decreased trend after the initiation of treatment. Conversely, PHA sfc showed an increased trend after 2 months of treatment. However, these indicators had moderate performance in distinguishing between before and after 6 months of treatment, and the AUC ranged from 0.702 to 0.839. Notably, the TBAg/PHA ratio in patients without risk factors was of important value in differentiation between before and after treatment. The optimal AUC of TBAg/PHA ratio reached up to 0.890. Patients with unsuccessful treatment outcomes showed persistently high levels of TBAg/PHA ratio. The TBAg/PHA ratio in patients after 6 months of treatment showed a certain potential in distinguishing between patients with successful and unsuccessful treatment outcomes. A further calculation of the TBAg/PHA ratio in T-SPOT assay has potential value in the treatment monitoring of TB, but further confirmation is needed.