In low- and middle-income countries (LMICs) including India, cancer patients have a poor prognosis because of late diagnosis and cases already grown to advanced stages, low cancer awareness and skewed cancer care facilities. In India, the incidence of colorectal cancer (CRC) is ranked the 4th most common (6.4%) in males and the 5th most common (3.4%) in females. The improvement in the cure rate of rectal cancer has increased life expectancy, and assessment of the quality of life (QoL) in these patients has become a fundamental requirement. Little is known about how the patients perceive these adverse effects during curatively intended radiotherapy. Although studies have investigated the various adverse effects that can occur with radiotherapy and chemotherapy in carcinoma rectum patients, these have not yet been critically appraised and synopsized to form a comprehensive review of their prevalence and effects on QoL. The study was designed to explore the QoL issues in locally advanced carcinoma rectum patients during various phases of neoadjuvant concurrent chemo-radiotherapy (NACCRT). The study was performed over a period of 2 years at a single super speciality cancer hospital in North India. Patients were selected as per the inclusion criteria and followed up with a standard questionnaire incorporating various aspects depicting QoL. The interview technique was used for collecting QoL data at four points, at baseline, midway during treatment, at the end of treatment and 4 weeks after completion of NACCRT, using EORTC QLQ C30, for QLQ CR29. Special care was taken to avoid observer bias in cases of language issues, and interpreters' services were utilised, and compared with the baseline pre-treatment scores, patients reported a statistically significant and large clinically meaningful change in the global health status, social functioning, fatigue (FACIT-F), appetite loss, anxiety, sore skin and male and female sexual function at the post-treatment time point. Statistically significant changes with moderate clinically meaningful changes were reported for the functional scales-physical, role and emotional functioning of the QLQ C30 questionnaire and body image and weight of the CR29 questionnaire. Similar moderate clinical changes were found in the symptom scales-fatigue, nausea and vomiting, insomnia, constipation and diarrhoea of QLQ C30 and stool frequency, embarrassment with bowel function, impotence and dyspareunia. These parameters returned to almost the pre-treatment values after 4 weeks of completion of NACRT. Since QoL is a relatively subjective variable, differences in human race, culture, education and social environment will have impacts on the results. International cooperation is needed to study the QoL in patients with multiple cultural backgrounds. The existing QoL questionnaire tools have been designed with Western countries in mind, and we did face multiple social issues. We suggest that many similar multicentre studies shall be required to essentially tap the accurate QoL-related issues keeping in mind the diverse social, economic, racial and educational backgrounds. As we deal with the ever-increasing cancer menace and better life expectancy, QoL issues shall be a major determinant of treatment success besides primary treatment. These factors should form an integral part of treatment modality, and adequate counselling must be performed prior to initiation of care.