Background: An animal study has shown that platelets form are formed in the lungs. Therefore, we wanted to study the relationship between lung radiation dose and platelet count in lung cancer patients receiving radiation therapy. Methods: This retrospective study included 93 patients with lung cancer who received radical thoracic radiation therapy. The correlation between pulmonary dose-volume histogram (DVH) parameters and thrombocytopenia during radiotherapy (RT) was evaluated by chi-square test, logistic regression analysis, Spearman and Pearson correlation analysis, etc. Results: Thrombocytopenia occurred in 17 of 93 patients (18.3%). Chi-square test and logistic regression analysis showed that chemotherapy (p = 0.038), MLD (mean lung dose, p = 0.001), V{}_5 (p = 0.008), V{}_{10} (p = 0.004), AND V{}_{20} (p = 0.003) were important independent predictors of thrombocytopenia. Using the chi-square test, increased MLD (p = 0.002), V{}_5 (p = 0.021), V{}_{10} (p = 0.008), and V{}_{20} (p = 0.006) were associated with increased risk of thrombocytopenia. Receiver operating characteristic (ROC) curve was used to analyze the thresholds of MLD, V{}_5, V{}_{10,} and V{}_{20}, which showed high sensitivity and specificity for distinguishing between non-thrombocytopenia and thrombocytopenia. Conclusions: Higher doses of radiation to the lung are associated with an increased risk of thrombocytopenia. Moreover, optimization of treatment plans via the control of DVH parameters may reduce treatment interruptions and improve outcomes in lung cancer patients treated with RT.