Docosa Hexaenoic Acid (DHA) is an essential fatty acid that plays major role in human health. It is typically extracted from fatty fish and this puts pressure on global fish stock. DHA obtained from fish is also prone to contamination. Schizochytrium is a potential alternative source, having the ability of accumulating considerable amounts of DHA. Modification of medium components and culture conditions are the preferred techniques to enhance DHA production by this marine microalga. In this study, two-level factorial design was employed to investigate the significance of sea salt, glucose, yeast extract, Monosodium Glutamate (MSG) and peptone in affecting the biomass, lipid and DHA accumulation processes of a locally isolated strain of Schizochytrium. In contrast to the conventional ANOVA method commonly employed in various screening studies, half normal probability plots were used to identify the significant factors, whereas interaction plots were used to explain the pattern of interaction between significant combinations. Design Expert software was used to construct a set of experiments where each medium component mentioned above was varied over two levels. Cultivation was carried out in 250 mL flasks containing 50 mL of medium, incubated at 30°C with 200 rpm agitation for 96 h. This experiment revealed that sea salt and interaction of glucose-MSG have significant effect on biomass production whereas sea salt and interaction of sea salt-glucose affected lipid accumulation. Meanwhile, interactions of glucose-yeast extract and glucose-MSG have significant effect on DHA accumulation. Detailed analysis of interaction plots enabled deeper understanding of the behavior of the system in response to the significant variables, which improves the precision in determination of variable domains for effective medium optimization.