Mucoproteins being essential and normal constituents of body tissues are widely distributed in the extra cellular matrix as ground substances. They are also present on cell surfaces and in connective tissues. Present study was carried out to authenticate the significance of serum mucoproteins as biomarkers and to know the effect of radiations on the levels of serum mu-coproteins, in head and neck malignant cases treated with standard dose of radiotherapy. 96 patients of head and neck malignancies, suffered from early and late stages, referred to Radiotherapy Department of Krishna Hospital, Karad (India) were selected and included in the study.63 volunteers served as healthy controls. Serum mucoproteins were estimated in malignant patients before initiation of radiotherapy and one month after completion of radiotherapy. Significant increased levels (P < 0.001) of serum mucoproteins were observed in malignant patients before radiotherapy, as compared to the levels of healthy controls. After one month of radiotherapy, the serum mucoproteins significantly (P <0.001) decreased in comparison to the pre treated serum mucoprotein val-ues. The fall in serum mucoprotein levels after radiotherapy showed much higher values in early stages than late stages of head and neck malignancies. The marked increased levels of serum mucoproteins in all the stages of head and neck ma-lignancies before radiotherapy and significant decreased serum mucoproteins after radio-therapy suggested serum mucoproteins as good biomarkers of neoplastic activity. The study concludes that the estimation of serum mucoproteins before and after radiotherapy serves as a significant biomarker in diagnosis and prognosis of head and neck malignancies.