OBJECTIVES: The current study was aimed to assess knowledge and awareness about thalassemia among the guardians of thalassemia patients of Quetta, Pakistan.  METHODS: The cross-sectional descriptive study was undertaken by using structured questionnaire in different Thalassemia Centers of Hospitals of Quetta, Pakistan from March to July 2016. Convenient sampling was adopted for data collection. A total of 327 Patients diagnosed with thalassemia major were included for study while patients taking oral Iron overload treatment were excluded. Descriptive and inferential statistics (Mann Whitney U test and Kruskal Wallis tests, p < 0.05) were used to assess the significance among study variables. Analysis were performed using IBM SPSS v.20. RESULTS: The result showed that mean age of the respondents were 35.5 ± 15.45 years and 154 (60.6%) were males. Majority of the respondents (n=97, 38.2%) had primary level of education and belonged to urban area (n=174, 78.55%). The results also showed majority (n=242, 96.9%) of respondents had adequate knowledge regarding thalassemia. Health care providers were reported as major source of thalassemia information by more than 75% of the study participants. Comparison of mean score showed that education level, occupation, area of residence had significant (p<0.05) associated with the knowledge score. CONCLUSIONS:  The study concluded that the guardians of the thalassemia patients had better understanding regarding their child diseases and this could be beneficial in better care of child.