Even traditional pretreatments can partially remove or degrade lignin and hemicellulose from lignocellulosic biomass for enhancing its enzymatic digestibility, the remaining lignin in pretreated biomass still restricts its enzymatic hydrolysis by limiting cellulose accessibility and lignin-enzyme nonproductive interaction. Therefore, many pretreatments that can modify lignin structure in a unique way and approaches to block the lignin’s adverse impact have been proposed to directly improve the enzymatic digestibility of pretreated biomass. In this review, recent development in sulfite pretreatment that can transform the native lignin into lignosulfonate and subsequently enhance saccharification of pretreated biomass under certain conditions was summarized. In addition, we also reviewed the approaches of the addition of reactive agents to block the lignin’s reactive sites and limit the cellulase-enzyme adsorption during hydrolysis. It is our hope that this summary can provide a guideline for workers engaged in biorefining for the goal of reaching high enzymatic digestibility of lignocellulose.