Neutropenia is the most common adverse reaction seen in small cell lung cancer after chemotherapy. Febrile neutropenia (FN) leads to an increase in hospitalizations and may even be life-threatening. This paper aims to investigate the efficacy and adverse reactions of mecapegfilgrastim in the primary prophylaxis of neutropenia in patients with small cell lung cancer after receiving intermediate risk chemotherapy with at least one patient risk factor. The clinical records of 106 patients with small cell lung cancer admitted to Zhejiang Cancer Hospital from June 2019 to January 2021 were retrospectively analyzed. Patients were divided into a mecapegfilgrastim [pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF)] group and control group, each with 53 patients. The mecapegfilgrastim group received subcutaneous injection of mecapegfilgrastim 24 hours after the first cycle of chemotherapy, while the control group did not receive this. The Chi-square (χ2) test or Fisher exact test were used to compare the incidence of neutropenia, FN, and the proportion of patients administrated with full dose chemotherapy in the two groups after the first cycle of chemotherapy. Data on adverse events after mecapegfilgrastim were also collected. After the first cycle of chemotherapy, the incidence of neutropenia in the mecapegfilgrastim group was significantly lower than that in the control group (P=0.001) and the incidence of FN in the mecapegfilgrastim group was lower than that in the control group (P=0.118). The proportion of patients administrated with full-dose chemotherapy in the mecapegfilgrastim group was significantly higher than that in the control group (P=0.001). The main adverse reactions to mecapegfilgrastim were muscle pain, fever, and fatigue. After receiving intermediate risk chemotherapy, the incidence of neutropenia was significantly reduced by the primary prophylaxis of mecapegfilgrastim in patients with small cell lung cancer. The adverse events of mecapegfilgrastim were mild and tolerable, and included muscle pain, fever, and fatigue.