Introduction: Sickle-cell disease (SCD) refers to a group of inherited disorders affecting hemoglobin resulting sickle hemoglobin variant (HbS). A simple, low-cost, paper-based test for SCD offers advantages over existing technologies for screening programs in resource-limited settings. The primary aim is to test the efficacy of paper-based test as a simple low cost and electricity free test. The main objectives are to determine the sensitivity and specificity of paper-based screening test for SCD in compare to HPLC test and to validate the paper based test. Materials and Method: A comparative study was conducted in the Dept. of Physiology from April to June 2021 as ICMR approved STS project, after obtaining the ethical clearance (SVIEC/ON/MEDI/SRP/20027). A total of 60 samples (n=60) were collected from individuals ranged between 18-40 years for the study. Blood samples collected in EDTA anticoagulant vacutainers were used for SCD diagnosis by using paper-based test and then confirmed by HPLC test, using HPLC test as the gold standard test. Result and Conclusion: True positive(TP), false positive(FP), true negative(TN), and false negative(FN) were determined on the basis of result obtained from HPLC test. The result obtained includes TP=36, FP=4, T N=10 and FP=10. The sensitivity and specificity of paper-based screening test was evaluated to be 78.2% and 71.4% respectively for HbS (HbAS and HbSS). ROC curve was obtained and the area under curve is 0.88 for discriminating between HbAA from HbAS and HbSS by paper-based test. In conclusion, the paper-based test can be used as a substitute for screening HbS. The study validates the paper-based test as a simple low-cost and electricity free test capable of detecting sickle cell trait and disease and demonstrate its practicality in resource-limited clinical settings.