In this paper, in order to construct a 3D quantitative structure-activity relationship (QSAR) model with the chlorobenzene (CB) molecular structure parameter as an independent variable and the octanol-water partition coefficient (K-OW) as a dependent variable, 9 kinds of CB molecules were used as training sets and 3 kinds of CB molecules were used as test sets. We adopted the QSAR module in the Sybyl-X2.0 software from the Tripos Corporation (USA). The molecular modification of the pentachlorobenzene molecule with low bioconcentration was carried out by combining a three-dimensional contour map and fractional factorial design. The results showed that the toxicity, migration, and enrichment of 17 new pentachlorobenzene molecules with low bioconcentration decreased and their degradability increased; it was also found that the concentration and amplification effect of the pentachlorobenzene molecules in the food chain decreased after modification when compared with unmodified pentachlorobenzene, which was determined by docking premodified and modified pentachlorobenzene molecules with enzymes in living organisms in a food chain ( Chlamydomonas reinhardtii -> Daphnia pulex -> Danio rerio -> pelican). Furthermore, the enrichment capacity of the modified pentachlorobenzene in some edible animals (such as pigs, cows, sheep, chickens, ducks, rabbits, and fish) also decreased.