OBJECTIVES: Schizophrenia negative symptoms (SNS) represent the major contributor to poor functional outcomes, loss in productivity and poor quality of life (QoL) of schizophrenic patients. It is unclear which instruments may be used for assessing QoL of such patients. SNS are characterized by severe withdrawal and paucity of speech, and communication making patients elicitation of perception difficult. The aims of this study were to identify the health related quality of life (HRQoL) instruments used in patients suffering from schizophrenia with predominant negative symptoms (NS) or mixed NS and to assess the level of validation of the instruments used to assess QoL of patient with SNS. METHODS: A systematic literature review was performed using the Medline database via PubMed. Studies with a QoL measure in schizophrenic patients published between 1989 and March 2016 were identified. The studies involving SNS patients were included, then, the instrument used was reported and a targeted research was performed to identify if a conceptual framework was performed, the instrument, psychometric proprieties were identified as well as the pivotal and successive validation if available. RESULTS: Seventeen HRQoL instruments used in SNS patients were identified including 3 generic questionnaires, 8 for nonspecific mental health questionnaires, and 6 specific for schizophrenia. Conceptual frameworks were identified for 4 instruments, reported as performed but not described for 3 and for 10 instruments they were no mentions of conceptual framework. No HRQOL specific to SNS population was identified. No data are reported for those SNS patients specifically. CONCLUSIONS: No QoL instrument has been validated in SNS patients and it is even unclear for all of them if they are conceived for capturing HRQoL in SNS patients. SNS are widely prevalent in schizophrenic patients but their impact on QoL remains unknown. This requires further research.