Cinobufacini is a Chinese medicinal preparation extracted from the traditional Chinese medicine toad skin and is commonly used clinically as an adjuvant treatment for malignant tumours. To systematically evaluate the effects of Cinobufacini combined with a first-line platinum-based chemotherapy regimen in patients with non-small-cell lung cancer (NSCLC), especially in terms of immune function. Eight electronic databases were searched for randomised controlled trials (RCTs) investigating Cinobufacini in conjunction with platinum-based chemotherapy for NSCLC (stage III-IV) published from 2012 to the present. GRADE Pro GDT was used to assess RCT quality and meta-analysis was performed mainly using Review Manager version 5.4, with the assistance of Stata version 16.0 (StataCorp LLC, College Station, TX, USA), and trial sequential analysis software. A total of 35 studies were included. Meta-analysis revealed that the combination therapy group exhibited a better disease control rate (DCR) OR = 2.63, 95%CI (2.15, 3.21), P < 0.00001, with a higher one-year OR = 2.41,95% CI (1.75,3.33), P < 0.00001, and two-year OR = 2.28, 95% CI (1.56,3.33), P < 0.00001 survival rate, plus lower leukocyte toxicity OR = 0.40, 95%CI (0.33,0.49), P < 0.00001. For immune function, the combination of chemotherapy with Cinobufacini effectively increased the proportion of CD3+ SMD = 1.15, 95% CI (0.89,1.42), P < 0.00001, CD4+ SMD = 1.60, 95%CI (1.26,1.94), P < 0.00001 and the CD4+/CD8+ ratio SMD = 2.15, 95% CI (1.45,2.86), P < 0.00001 in peripheral blood. The addition of Cinobufacini to platinum-based chemotherapies for advanced NSCLC significantly improved clinical efficacy, enhanced immune function, and reduced chemotherapeutic toxicity, irrespective of administration and treatment duration.