The invention discloses a production process of super-soft-smooth anti-pilling and skin-friendly CVC single jersey. The production process comprises the following steps: spinning, weaving, pretreatment, peracid deoxygenization, polyester dyeing, reduction, cleaning, polishing, cotton dyeing, post-treatment, finishing and shaping. According to the production process, 75%-85% of cotton and 15%-25% of polyester are blended to form yarns, the yarns are woven by virtue of a Siro weaving process to form blank cloth, and the production is carried out according to certain production process and sequence; and finally the produced product has clear cloth marks, very good ventilation and perspiration effects and high glossiness, and a fabric has very good softness and soft and smooth hand feel and is skin-friendly and comfortable to wear. The production process has the beneficial effects that the operation is simple, complicated and expensive equipment is not required, the adopted raw materials are wide in source and low in cost, and the production cost is low.