Lung cancer is the leading cause of cancer death and second most common cancer diagnosed in both genders. In the US, 1 in 16 people will be diagnosed with lung cancer in their lifetime. Small cell lung cancer (SCLC) is a subgroup of lung cancers which account for 15% of cases. SCLC is the most fatal lung cancer subtype with a five-year survival rate of only 7%. Due to the tendency of developing metastases early and often in SCLC, even localized disease required systemic therapy with both chemotherapy and radiation. SCLC relapse commonly occurs within months after treatment and disease is typically resistant to further therapy. TRAF2 and NCK-interacting protein kinase (TNIK) has been found to play a role in radiation resistance in lung squamous cell cancer. Here, we investigate the role of TNIK and mechanism of radiation resistance in SCLC. Using different cell lines with high and low TNIK expression and the small molecule TNIK inhibitor, NCB-0846, we found that the TNIK expression appears to confer radiation resistance. Minimally, the mechanism of radiation resistance in SCLC appears to involve ATM-Chk2 DNA damage response pathway activation after radiation exposure in TNIK high cell lines. Other molecular mechanisms we are exploring involve radiation-induced cell cycle checkpoints. Overall, our findings suggested that TNIK might be a therapeutic target and can confer radio-resistance in SCLC.