This experiment was conducted to discuss the effects of diets with different protein source combinations on growth performance and serum biochemical indices of weaner piglets. According to similar age and weight, a total of 200 weaner piglets were randomly divided into five groups, each group had 4 replicates and each replicate had 10 piglets. The experiment was divided into 2 phases: creep phase (21 to 33 days of age) and starter phase (34 to 55 days of age). In the creep phase, experimental design was as follows: piglets in the control group were fed a basal diet containing 4% spray-dried plasma protein, piglets in experimental groups Ⅰ, Ⅱ, Ⅲ and Ⅳ were fed the diets containing 3% wheat germ protein hydrolysates + 2% imported yeast extract, 5% casein, 3% isolated soybean protein + 2% imported yeast extract, 3% soybean protein isolate + 2% domestic yeast extract to replace spray-dried plasma protein in the basal diet, respectively, and this experiment lasted for 12 days. After creep phase, all piglets were translated into the starter phase, and fed the same starter diets. This experiment lasted for 21 days. The results showed as follows: 1) in the two phases, the average daily feed intake (expect for experimental group Ⅰ in creep phase), feed/gain and diarrhea rate in experimental groups had no significant differences compared with the control group (P>0.05); the average daily gain in experimental group Ⅰ in the creep phase was significantly lower than that in the control group (P<0.05), while the experimental group Ⅲ was significantly higher than the control group (P<0.05), and the crude protein apparent digestibility in experimental group Ⅰ was significantly lower than that in the control group (P<0.05). In the starter phase, the crude protein apparent digestibility in experimental group Ⅰ was significantly lower than that in the control group (P<0.05), however, the experimental group Ⅳ was significantly higher than the control group (P<0.05). 2) On 33 days of age, compared with the control group, the contents of total protein, albumin, globulin, urea nitrogen and glucose, albumin/globulin, and the activities of glutamic-pyruvic transaminase and glutamic-oxal (o) acetic transaminase in serum in the experimental groups had no significant differences (P>0.05). The immunoglobulin G content in experimental group Ⅱ was significantly lower than that in the control group (P<0.05), but immunoglobulin A and immunoglobulin M contents were significantly higher than those in the control group (P<0.05). It is concluded that 3% wheat germ protein hydrolysates + 2% imported yeast extract, 5% casein, 3% isolated soybean protein + 2% imported yeast extract, 3% isolated soybean protein + 2% domestic yeast extract can replace spray-dried plasma protein in the basal diet, which do not affect the growth performance of weaner piglets.