According to UNICEF there are 220,000 adolescents infected by HIV/AIDS in India. In which around 70,000 adolescents are below the age of 15 and 21,000 adolescents are being infected through mother-child transmission every year. "A quasi experimental study to evaluate the effectiveness of 'Holistic Humanized Nursing Care strategy' on physiological parameter of adolescents living with HIV in selected settings". Quantitative research approach was adopted, quasi experimental research which includes control group and manipulation with no randomization. The settings of the study were Integrated Child Welfare Organization (ICWO), Thiruvallur. The sample consist of 40 adolescents in experimental and control group who were diagnosed to have HIV and met inclusion criteria and chosen by non probability purposive sampling technique. The tool used was a demographic variables and HIV related Fatigue scale(HRFS) for assessing physiological parameter ( Fatigue).The calculated paired t value of t is = 4.91 was found to be statistically significant at p < 0.001 level. It clearly indicates that after the administration of Holistic Humanized Nursing Care strategies there was significant increase in the physiological parameter (Fatigue) in the experimental group. The calculated paired t value of t = 0.64 was not found to be statistically significant and this clearly indicates that there was no significant increase in the level of physiological parameter (Fatigue) in the control group. The calculated value of Z was = 3.34 between experimental and control group was found to be statistically significant at p ,<0.001level.This clearly indicates that the Holistic Humanized Nursing care strategies to the adolescents with HIV was found to be effective to increase the physiological parameter(Fatigue) among adolescents with HIV in the experimental group than the adolescents in the control group.