Objective. To analyze the expression and clinical significance of miR-204 in the serum of patients with severe pneumonia (SP) and primary bronchial lung cancer (LC). Methods. 65 SP patients and 43 primary bronchial LC patients who were treated in the hospital from January 2017 to December 2018 were randomly selected as the SP group and LC group. At the same time, healthy patients from the physical examination department of the hospital were selected. 65 cases were the control group. QRT-PCR detected serum miR-204 expression and compared the differences between groups. The pathological data of patients were collected, and the relationship between serum miR-204 and the patient’s pathological data was compared; the area under the ROC curve and Kaplan–Meier curve were used to evaluate the diagnostic value of serum miR-204 for the two conditions and to explore the relationship between serum miR-204 and prognosis. Results. The serum miR-204 of the SP group was (0.43 ± 0.09), the serum miR-204 of the LC group was (0.40 ± 0.10), the serum miR-204 of the control group was (1.00 ± 0.09), and the miR-204 level of was significantly higher than that of the control group, and the difference between the groups was statistically significant (
P
< 0.05). There was no significant difference in serum miR-204 levels between the SP group and the LC group (
P
> 0.05). Serum miR-204 levels in SP patients with cumulative organs ≥3 were higher than those with cumulative organs <3, and the difference was statistically significant (
P
< 0.001). In the LC group, in patients with stage III to IV and low and undifferentiated patients, the level of miR-204 was higher than that of stage I∼II and high and moderately differentiated patients, and the difference was statistically significant (
P
< 0.001). The level of miR-204 in the two groups of patients (0.89 ± 0.10, 0.83 ± 0.13) who died of illness was significantly higher than that of the surviving patients (1.00 ± 0.11, 1.00 ± 0.10), and the difference was statistically significant (
P
< 0.05); the survival rate of patients with high expression of miR-204 was higher than that of patients with low expression. The AUC of serum miR-204 level to SP and LC was 0.766 and 0.818, respectively. Conclusion. The level of miR-204 in the serum of SP patients and patients with primary bronchial LC was significantly lower than that of healthy people, and patients who died were lower than those who survived; the miR-204 in serum has a good diagnostic value for SP and LC and is related to the survival and prognosis of patients.