<p indent=0mm>Applying membrane scaling is a key problem in reverse osmosis (RO) desalination processes. By dosing antiscalant, we can effectively inhibit inorganic scale and control RO membrane scaling. Accordingly, in this work, an environmentally friendly modified cellulose-based antiscalant is synthesized by the etherification of cellulose and subsequent graft copolymerization using the etherification product carboxymethyl cellulose (CMC), acrylic acid (AA), and sodium allyl sulfonate (SAS): CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS). The influence of molecular structure, CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS) dose, and coexisting anions with respect to inhibiting the calcium-sulfate scale in the RO system are investigated. The results indicate that dosing CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS) can significantly prolong the induction time of calcium-sulfate crystallization, inhibit the formation of calcium-sulfate scale, greatly alleviate both membrane fouling and membrane flux decline caused by membrane-surface scale formation, and effectively improve the membrane filtration efficiency. Static tests, scanning electron microscopy, optical microscopy, X-ray diffraction, conductivity measurements, and dispersion experiments suggest that the scale inhibition mechanism of CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS) can be attributed to the chelation and dispersion effects of the introduced anionic groups, and that the carboxyl groups are more efficient in the inhibition of calcium-sulfate scale than the sulfonic groups. In addition, an appropriate number of sulfonic groups on the graft chain of CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS) can improve the water solubility of CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS), as well as effectively stabilize the scale-formed substances and enhance the scale inhibition efficiency. If the proportion of sulfonic groups is too high, the content of the carboxyl groups decreases accordingly, which reduces the chelation and dispersion effects of CMC-<italic>g</italic>-P(AA-<italic>co</italic>-SAS), which, in turn, reduces the scale inhibition performance.