Background and Purpose : Neoadjuvant chemoradiation (CRT) is the mainstay treatment for locally advanced rectal carcinoma. However, the response is varied due to many factors, including tissue hypoxia. Osteopontin (OPN) is an emerging endogen hypoxic marker with significant correlation towards tumor pO2, also a more accurate chronic hypoxic marker compared to carbonic anhydrase IX (CAIX), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA); but as far as we know there is no research that measured OPN quantity in rectal cancer tissue and correlated it with tumor shrinkage response in neoadjuvant CRT. Materials and Method : Fourteen patients that met the inclusion and exclusion criteria were analyzed retrospectively. Imaging was evaluated for tumor shrinkage percentage and categorized based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. OPN level quantitative results from rectal cancer tissue were obtained using ELISA method. Results : The mean OPN concentration was 0.568 ± 0.26 ng/mL. There was a significant strong negative correlation ( r = −0.630, p = 0.016) between the OPN level and tumor shrinkage. OPN cut off value of ≥0.538 ng/mL predicted non-responsiveness of tumor shrinkage in neoadjuvant CRT with 100% sensitivity and 81.8% specificity. Conclusion : Hypoxia occurred in locally advanced rectal carcinoma patients. Higher level of OPN correlates negatively with tumor shrinkage, proved worse response of CRT given.