Aim of the present work was to prepare the colon-targeting pH dependent microcapsules of Thymoquinone for the treatment of colorectal cancer. pH dependent polymer Eudragit L100,and S100 were used to formulate the microcapsules by solvent evaporation technique using two methods. Microcapsules were evaluated for particle size, shape, flow properties, surface morphology by scanning electron microscopy, percentage yield, drug content, and in vitro drug release behaviour, in vivo targeting efficiency. The formulated microcapsules were discrete, almost spherical with somewhat folded and invaginated surface, and with good flow properties. Thymoquinone loaded microcapsules demonstrated good entrapment efficiency (of 86.438% in method 1 and 92.49% in method 2). Result of in vivo targeting efficiency showed that the formulation can able to target colon effectively. Formulation done by method 2 gave most promising result compared to first method. It is concluded from the present study that pH dependent Eudragit microcapsules are promising carriers for oral colon-targeted delivery of Thymoquinone for colorectal cancer.