Purpose The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) have been used as first line treatment in advanced Non-Small Cell Lung Cancer (NSCLC) with sensitive EGFR gene mutations. In clinical practice, we found that the rate of EGFR gene mutation in patients with Yin-cold syndrome type in traditional Chinese medicine (TCM) theory was higher than those with Yang-heat type syndrome. The purpose of this study was to identify the relationship between the TCM syndrome type and the EGFR gene status as well as efficacy of EGFR-TKIs in NSCLC patients. Methods From March 2013 to January 2014, we prospectively studied all the patients who are newly diagnosed with NSCLC without prior anticancer therapy, or those with recurrence with an interval of more than 6 moths from last anticancer therapy to the recurrence. The symptoms and signs which can help for the TCM syndrome type diagnosis were recorded. The EGFR gene statuses were also tested. The Yang-heat or Yin-cold syndrome types of TCM were diagnosed respectively by 3 TCM experts of our hospital to decide the TCM syndrome type. The relationship between the EGFR gene status and the TCM syndrome type were analyzed. The patients were followed up until August 2014. Results A total of 73 consecutive patients were enrolled in our study. 32 patients (43.84%) were with the Yin-cold syndrome type according to the TCM theory, while the other 41 patients (56.16%) were with the Yang-heat type. 17 patients (53.13%) in the Yin-cold group, while only 10 patients (24.39%) in the Yang-heat group, were with sensitive EGFR gene mutation (p=0.0120). 1 in the Yin-cold group and 1 in the Yang-heat group were with T790M at the exon 20 of EGFR gene. The EGFR genes were wild type in the other 44 patients. No significant difference was seen in PFS or OS between the TCM syndrome groups for those 22 patients who took EGFR-TKIs. Conclusion Patients with Yin-cold TCM syndrome type have more chance with sensitive EGFR gene mutation. However, no relationship was seen between the efficacy of EGFR-TKIs and TCM syndrome type.