To be clinically useful, an instrument assessing health-related quality of life (HRQOL) should be easy to understand and quick to answer. Few instruments have been designed to be short, simple, and easily understandable by patients from all educational levels. The aim of the present study was to evaluate the psychometric properties of a brief general instrument developed to assess HRQOL. Results from a preliminary study regarding the initial development of the Barretos Short Instrument for Assessment of Quality of Life (BSIqol) with 80 cancer patients are presented. Out of all the patients, 59 completed the BSIqol on two occasions in order to evaluate the reproducibility test-retest. Validity analyses were done comparing scores from BSIqol with EORTC QLQ-C30 and Edmonton Symptom Assessment System (ESAS). In addition, BSIqol scores were analyzed in function of ECOG-PS, work activity, and financial income. BSIqol demonstrated good internal consistency (Cronbach's α = 0.79) and adequate test-retest reliability, with intraclass coefficient correlation (ICC) varying from 0.736 to 0.946. There were adequate correlations between scores of BSIqol, EORTC QLQ-C30 and ESAS. The BSIqol was capable of discriminating between clinical subgroups, with different ECOG-PS and work activity. Patients completed the BSIqol in a median time <2 min. Only one patient reported some difficulty to answer the instrument. BSIqol seems to be a straightforward and useful instrument for rapidly assessing HRQOL from cancer patients. Further studies are necessary to evaluate BSIqol in different populations and also to assess its responsiveness and define its minimal clinically important differences.