Mushroom production could be used in protecting of the environment from different pollutants. Water hyacinth (Eichhornia crassipses) is one of the world‟s worst invasive weeds that caused a serious problem in different aquatic environment including Lake Tana. Many countries have prevented the impact of this invasive weed via variety mechanisms such as physical removal method, chemical and biological method (Julien et al., 2001). Among biological method one means is protected it via using of it as a substrate for mushroom cultivation with obtaining of nutritional rich food such as mushroom (Olal et al., 2001). This option was not yet tried in Ethiopia. Therefore the objective of this study was to evaluate the use of water hyacinth biomass and its combination with, wheat (Triticum aestivum) and teff (Eragrostis tef) straw at different mixing ratio for the cultivation of oyster mushroom (Pleurotus ostreatus).The experiment was set up in a Completely Randomized Design (CRD). The spawn of Pleurotus ostreatus was obtained from Addis Ababa city. Water hyacinth was collected from Lake Tana and the straws (teff and wheat) were collected from local farmers in different rural parts of Bahir Dar. The data were analyzed using SPSS version 26 with one- way analysis of variance (ANOVA) including Tukey test at (P≤0.05) and the data were presented with tables. The results of this study revealed that, the type of substrate significantly affected the time required for mycelium invasion, pinhead formation, first harvest starting, cap diameter, as well as stalk length, total yield and biological efficiency of Pleurotus ostreatus (P≤0.05). The shortest day that took for mycelium colonization and pinhead formation were recorded from wheat and teff straw respectively. The highest yield and biological efficiency were recorded from 100% wheat straw, while the lowest were observed from 100% teff straw. Using water hyacinth can be recommended as a substrate rather than wheat straw due to its dual purpose. Keyword: Biological efficiency, Lake Tana, oyster mushroom, water hyacinth